Dear colleague, Here is my attempt to collect the "important" information about the hematological disorders we have covered. Even though I did my best to extract these information from the sources below and to re-arrange them in an easy-to-understand method, the original textbooks remain as the pure reference for students to get their knowledge from. I wish you all the best in your life and thereafter,,, And don't forget to pray for me  Regards,

Done by: Ahmed Alsolami



Essential Hematology (A.V. Hoffbrand) Robbins Basic Pathology Davidson's Principles & Practice of Medicine Hematology at a Glance Danish Textbook of Medicine (Chapter of Blood Disorders)

Ahmed Alsolami <dr.solami@gmail.com>

Hemopoiesis diagram White blood cells Benign disorders of white cells Types of anemias-scheme Symptoms & Signs of Anemia Microcytic Hypochromic anemia Iron deficiency anemia Sideroblastic anemia Lead poisoning Anemia of chronic diseases Normocytic Normochromic Anemia Aplastic anemia Macrocytic Anemia Megaloblastic anemia Hemolytic Anemia Hereditary spherocytosis Thalassemia Sickle cell anemia G6PD deficiency Autoimmune hemolytic anemia Alloimmune hemolytic anemias Non-immune hemolytic anemias Leukemia Acute leukemias Acute lymphoblastic leukemia Acute myeloid leukemia Chronic myeloid leukemia Chronic lymphoblastic leukemia Lymphomas Hodgkin's lymphoma 3 4 5 8 9 10 10 10 11 12 13 13 15 15 18 20 21 23 24 25 26 27 29 30 30 31 32 33 34 34 Non-Hodgkin's lymphoma Myelodysplasia Myeloproliferative disorders Polycythemia rubra vera Essential thrombocythemia Myelofibrosis Multiple myeloma Bleeding disorders Vascular bleeding disorders Thrombocytopenia Platelet dysfunction Coagulation disorders 35 37 38 39 40 41 43 44 45 46 49 49

Ahmed Alsolami <dr.solami@gmail.com>

Diagrammatic representation of the bone marrow pluripotent stem cell and the cell lines that arise from it

Ahmed Alsolami <dr.solami@gmail.com>

White blood cells
Function of white cells:
Their primary function is to protect the body against infections. The white blood cells (leucocytes) may be divided into two broad groups: 1. Phagocytes (neutrophils, esinophils, basophils & monocytes)  they ingest and destroy pathogens and cell debris. 2. Immunocytes (lymphocytes, their precursor cells & plasma cells)  responsible for both the humoral and cellular specific immunity.

• • • Neutrophils (polymorphs): They are the most numerous peripheral blood leucocyte. Esinophils: They are particularly important in the response to parasitic and allergic diseases. Basophils: They are the least numerous peripheral blood leucocyte. They play an important part in immediate hypersensitivity reactions. In the tissues they become mast cells. Monocytes: In tissues they become macrophages.

• • • B-lymphocytes: They mediate humoral or antibody-mediated immunity T-lymphocytes: They mediate cell-mediated immunity Plasma cells: These are mature B-lymphocytes after their activation and release of membrane-bound immunoglobulins. They have a specific memory for certain pathogens.

Ahmed Alsolami <dr.solami@gmail.com>

Benign disorders of white cells
 Neutrophilia: increase in circulating neutrophils above the normal level. It can be caused by: 1. Bacterial infections (especially pyogenic bacteria) 2. Inflammation & tissue necrosis, e.g. vasculitis, MI, trauma 3. Metabolic disorders, e.g. uremia, acidosis, gout, eclampsia, DKA 4. Neoplasms of all types, e.g. carcinoma, lymphoma, melanoma 5. Acute hemorrhage or hemolysis 6. Drugs, e.g. corticosteroid therapy, tetracycline, lithium 7. Chronic myeloid leukemia & myeloproliferative disorders 8. Pregnancy

 Esinophilia: increase in circulating esinophils above the normal level.
It can be caused by: 1. Allergic diseases, e.g. asthma, hay fever, urticaria, food allergy 2. Parasitic diseases 3. Skin diseases, e.g. psoriasis, drug rash 4. Drug sensitivity 5. Connective tissue disease 6. Hematological malignancy, e.g. Hodgkin's lymphoma 7. Idiopathic hyperesinophilia 8. Esinophilic leukemia  Basophilia: increase in circulating neutrophils above the normal level. It is uncommon but occurs in myeloproliferative disorders.  Monocytosis: increase in circulating monocytes above the normal level. It can be caused by: 1. Chronic bacterial & protozoal infections 2. Connective tissue disease, e.g. SLE, RA, temporal arteritis 3. Chronic neutropenia 4. Myelodysplasia 5. Hodgkin's disease, acute myeloid leukemia & other malignancies
Ahmed Alsolami <dr.solami@gmail.com>

megaloblastic anemia. Hodgkin's lymphoma 4. Thyrotoxicosis  Lymphopenia: decrease in circulating neutrophils below the normal level. myelodysplasia. Kostman's syndrome ii. e. e. brucellosis. Non-Hodgkin's lymphoma 5. e. HIV. Widespread irradiation 6 Ahmed Alsolami <dr. Decreased production: • General bone marrow failure. Drug-induced. Cyclical iii. Acute lymphoblastic leukemia 3. Bone marrow failure 2. Corticosteroid and other immunosuppressive therapy 3. toxoplasmosis. e. hypersplenism Specific. It can be caused by: 1.com> . Neutropenia: decrease in circulating neutrophils below the normal level. chlorpromazine. It can be caused by: 1. syphilis • 2. Increased destruction: • • General. CMV.g. Congenital. Infections: • Acute: infectious mononucleosis. e. chemotherapy. clozaril. It can be caused by: 1. diuretics. pertussis. autoimmune-alone or in association with connective tissue disorder as RA (Felty's syndrome) •  Lymphocytosis: increase in circulating lymphocytes above the normal level.g. replacement by tumour Specific failure of neutrophil production: i. neomercazole. mumps. herpes simplex or zoster Chronic: TB. acute leukemia.g. infectious hepatitis. gold 2. rubella.solami@gmail.g. sulfonamides. Aplastic anemia. Chronic lymphoid leukemias 4.g.

3. 2.  Leukocyte adhesion deficiency type 2 (LAD2): There is defective synthesis of a selectin receptor  impaired adhesion to activated endothelium. phagocytosis and generation of an oxidative burst. spreading. Defects in microbicidal activity:  Chronic granulomatous disease: Deficiency of one component of the NADPH oxidase pathway responsible for generating superoxide  impaired activation of oxygen-dependent killing mechanism after engulfment of bacteria as it supposed to occur. Defects of phagocytic cell function: 1.com> . Defects in adhesion:  Leukocyte adhesion deficiency type 1 (LAD1): There is defective synthesis of leukocyte integrins  impaired adhesion. to differentiate between the leukomoid reaction & chronic myeloid leukemia which shows the same leucocytosis picture: • • Leukomoid reaction  ↑ Neutrophil alkaline phosphatase (NAP) score Chronic myeloid leukemia  ↓NAP score 7 Ahmed Alsolami <dr. Defects in phagolysosome formation:  Chediac-Higashi syndrome: Disordered intracellular trafficking of organelles  impaired lysosomal degranulation into phagosomes.solami@gmail.g. myeloblasts and myelocytes. severe hemolysis or metastatic cancer  excessive increase of leucocytes & accompanied by the presence of immature cells e. BUT.  Leukomoid reaction: Severe or chronic infections.

com> .B12 deficiency Folate deficiency Non-Megaloblastic Physiologic D/D : • • Pregnancy New born • • • • • • • Pathologic D/D : Alcohol Liver disease Hypothyroidism Myelodysplasia Aplastic anemia Multiple myeloma Reticulocytosis 8 Ahmed Alsolami <dr.solami@gmail.Types of Anemia Microcytic Hypochromic D/D : • • • • Iron deficiency Thalassemia Sideroblastic Chronic diseases • • • • • Normocytic Normochromic D/D : Many hemolytic anemias Acute blood loss Aplastic anemia Myelofibrosis Bone marrow failure (postchemotherapy. infiltration by carcinoma) Endocrine disorders Chronic diseases Macrocytic • • Megaloblastic D/D : • • Vit.

solami@gmail.com> .Symptoms & Signs of Anemia Symptoms: • • • • • • • Exertional dyspnea Fatigue Palpitation Headache Angina (in older patients) Intermittent claudication (in older patients) Visual disturbances (in severe anemia) Signs: • General : o Pallor o Tachycardia o Bounding pulse o Signs of heart failure (in older patients) • Specific : o Koilonychia  Iron deficiency anemia o Jaundice  Hemolytic or Megaloblastic anemia o Leg ulcer  Sickle cell anemia or spherocytosis o Bone deformities  Thalassemia major or other severe congenital hemolytic anemias suggest Excess infections Spontaneous bruising Neutropenia and Thrombocytopenia Possibly due to Bone Marrow Failure 9 Ahmed Alsolami <dr.

Menorrhagia)  most common ↑demand (infancy.Microcytic Hypochromic Anemia  Iron deficiency anemia : Causes: • • • • Chronic blood loss (GI bleeding. when 15% or more of the erythroblasts are ring sideroblasts in the bone marrow  Sideroblastic anemia is diagnosed.solami@gmail. atrophic gastritis) Poor intake Clinical features: • • General symptoms and signs of anemia (see page9) Manifestation of iron deficiency : o Brittle hair and nails o Atrophy of the tongue papillae o Angular stomatitis o Plummer Vinson syndrome (Iron def.com> . gastrectomy. 10 Ahmed Alsolami <dr. pregnancy. anemia + Dysphagia) Laboratory findings : See the table on page12  Sideroblastic Anemia Defect in the enzyme ALA synthase  ineffective utilization of iron to form haem  iron accumulate in erythroblasts in the bone marrow  formation of a ring of iron granules around the nucleus  Ring Sideroblasts. lactation) ↓absorption (celiac disease. adolescence.

Megaloblastic anemia.g.solami@gmail. isoniazide o Alcohol o Lead poisoning o Benign conditions (e.g. malabsorption. myeloma) o Drugs: antituberculous e. 11 Ahmed Alsolami <dr.Causes : • • • Hereditary: (X-Linked ) occur independently without any other disease. causing its accumulation in the cytoplasm. Laboratory findings : See the table on page12  Lead Poisoning Hemolytic (predominant) Lead poisoning causes anemia which is either Hypochromic It does so by inhibiting both haem & globin synthesis at several points. hemolytic anemia.g. rheumatoid arthritis) Manifestation : • • Signs & symptoms of anemia (see page9) Manifestation of the secondary causes if found.com> . Primary: (one subtype of Myelodysplasia). Myelofibrosis. Secondary: sideroblastic anemia may also occur with : o Malignant diseases of the marrow (e. myeloid leukemia. Characteristic features of lead poisoning : o Ring sidroblasts in bone marrow o Basophilic Stippling in the RBCs (deep-blue dots in the cytoplasm under staining) because lead interferes with the enzyme responsible for RNA degradation. which under staining gives this appearance.

sarcoma).g. osteomyelitis. Laboratory diagnosis of hypochromic anemia.g. Iron deficiency Chronic diseases Normal or mild ↓ ↓ ↓ Normal/↑ Present Absent Normal Thalassemia Sidroblastic trait (α or β) ↓ in congenital type. • • Causes : • Chronic inflammatory diseases: o Infections (e. Anemia of chronic diseases Pathogenesis: it occurs in relation to: • Decreased release of iron from macrophages (due to Hepcidin release by the liver in response to inflammation  inhibition of iron release from macrophages as well as iron absorption) Inadequate erythropoietin response to anemia (due to the effect of cytokines such as IL-1. o Non-infectious (e. TNF on erythropoiesis) Reduced red cell lifespan. but MCV often ↑ in acquired type ↑ Normal ↑ Present Ring forms Normal MCV & MCH ↓ ↓ Serum iron TIBC Serum ferritin Bone marrow iron stores Erythroblast iron Hemoglobin electrophoresis ↓ ↑ ↓ Absent Absent Normal Normal Normal Normal Present Present ↑ Hb A2 in β form 12 Ahmed Alsolami <dr.g. SLE. pulmonary abscess. RA. • Malignant diseases (e. pneumonia.com> . bacterial endocarditis). Crohn's disease).solami@gmail. lymphoma. carcinoma. sarcoidosis. TB.

infiltration by carcinoma. cyclophosphamide.solami@gmail. Chronic diseases  Aplastic anemia It is a disorder characterized by the suppression of multipotent myeloid stem cells (that have the capacity to differentiate into RBCs.com> . Endocrine disorders (Hypopituitarism.Normocytic Normochromic Anemia Causes : • • • • • • • Many hemolytic anemias Acute blood loss Aplastic anemia Myelofibrosis Bone marrow failure (post-chemotherapy. 13 Ahmed Alsolami <dr. hypoaldosteronism). hypothyroidism. viral hepatitis) o Paroxysmal nocturnal hemoglobinuria (PNH) Aplastic anemia usually presents with symptoms and signs of pancytopenia. insecticides) o Drugs (busulfan. U Causes : • Primary : o Congenital (Fanconi and Non-Fanconi types) o Idiopathic acquired (autoimmune) • Secondary (direct damage to the hemopoietic marrow) : o Chemicals (benzene. myeloma). WBCs or platelets). chloramphenicol) o Ionizing radiation o Viruses (EBV.

solami@gmail. bleeding gums. menorrhagia). epistaxis. ↓Platelets (Thrombocytopenia). Bone marrow shows hypoplasia. TB o Megaloblastic anemia o Paroxysmal nocturnal hemoglobinuria (PNH) • Increased peripheral destruction : o Hypersplenism Laboratory findings : • • • • • Normochromic anemia. Extreme↓in reticulocyte count. ↓WBCs (Leucopenia) especially granulocytes.com> . myelodysplasia. Other causes of pancytopenia : • Decreased bone marrow function: o Aplasia o Acute leukemia. myeloma o Infiltration with lymphoma. 14 Ahmed Alsolami <dr. but either normocytic or macrocytic.Manifestations of aplastic anemia (pancytopenia) : • • • ↓RBCs  symptoms of anemia (see page9) ↓WBCs  Impaired immunity  infections (mouth & throat) ↓Platelets  Bleeding tendency (bruising. with loss of hemopoietic tissue and replacement by fat which comprises over 75% of the marrow. myelofibrosis. solid tumors.

• Causes of Vit.B12 or Folate deficiency  ↓DNA synthesis  slow erythroblast maturation  cell division is decreased but cytoplasmic maturation progresses  large cell with ↓DNA mass ( ↑ RNA/DNA ratio) which is called "Megaloblast"  these cells are destroyed in bone marrow  the bone marrow becomes hypercellular to compensate for the destruction. but the RBC production is still severely reduced " Ineffective Erythropoiesis".Macrocytic Anemia Macrocytic anemia is subdivided into Megaloblastic and Non-megaloblastic based on the appearance of the developing erythroblasts in the bone marrow U  Megaloblastic anemia : • Vit.B12 deficiency : • • Nutritional : Vegetarian diet Malabsorption : o Gastric causes :    Pernicious anemia Congenital lack or abnormality of Intrinsic Factor Total or partial gastrectomy o Intestinal causes :     Ileal resection or Crohn's disease Chronic tropical sprue Bacterial overgrowth Fish tapeworm 15 Ahmed Alsolami <dr. WBC & platelet production are also affected  Pancytopenia.com> .solami@gmail.

spina bifida. myeloma) Inflammatory diseases (e. trimethoprim) o Anticonvulsants. RA) Excess urinary folate loss : o Active liver disease o Congestive heart failure • Drugs : o Antifolate drugs (e. difficulty in walking and loss of proprioception.com> • . 16 Ahmed Alsolami <dr.B12 deficiency) Neural tube defect : deficiency of Vit. methotrexate. Purpura due to thrombocytopenia is less frequent. Sulfasalazine Manifestation of Megaloblastic anemia : • • • • • Gradually progressive symptoms and signs of anemia (see page9) RBC destruction  Mild jaundice.g. TB.solami@gmail. Prematurity o Pathological :    • Hematological diseases (e.Causes of folate deficiency : • • Nutritional Malabsorption : o Tropical sprue. gluten-induced enteropathy • Excess utilization : o Physiological :  Pregnancy. (only with Vit. angular stomatitis.g. mild symptoms of malabsorption and loss of weight. lactation. myelofibrosis) Malignant diseases (e.g. Crohn's disease. Epithelial abnormality  Glossitis. Neuropathy : the patient feels tingling in the feet.g. phenytoin. carcinoma. encephalocoele).B12 or Folate in the mother predisposes to neural tube defect in the fetus (anencephaly. hemolytic anemias. lymphoma.

B12 absorption test.Laboratory findings: • CBC : o ↑MCV o ↓reticulocyte count o WBC & platelet are moderately ↓ o Neutrophils show hypersegmented nuclei • • • • • Bone marrow is hypercellular and the erythroblast are enlarged "Megaloblasts".com> .solami@gmail. due to RBC breakdown. (Schilling test). Vit. 17 Ahmed Alsolami <dr. ↑serum unconjugated bilirubin and lactate dehydrogenase (LDH).  Non-Megaloblastic anemia: Refer to the diagram on page8 to see the causes.B12 In Folate deficiency  ↓folate in serum and RBC. In VitB12 deficiency  ↓serum Vit.

Hemolytic anemia  Laboratory findings in hemolytic anemia: • Features of increased RBC breakdown: o ↑serum unconjugated bilirubin o ↑urobilinogen o ↑stercobilinogen o ↑ uric acid & lactate dehydrogenase LDH o ↓serum haptoglobin. because it binds to the released hemoglobin and the complex is removed by the reticuloendothelial system. o Hemoglobinuria o Hemosiderinuria • Features of increased RBC production: o Reticulocytosis o Bone marrow erythroid hyperplasia o Bone deformity due to marrow overexpansion These findings can be found in any hemolytic anemia but they vary from one disease to another.  Intravascular and Extravascular Hemolysis: • Intravascular Hemolysis is due to: o Mismatched blood transfusion o G6PD deficiency o Microangiopathy o Some autoimmune hemolytic anemias o PNH o March hemoglobinuria o Some drug-induced or infection-induced (e.com> .g. Thus. Falciparum Malaria) 18 Ahmed Alsolami <dr.solami@gmail. prominent features of each hemolytic disease will be mentioned correspondingly.

burns. thalassemia Acquired Immune: Autoimmune:  worm Ab type. clostridia Secondary:  liver or renal disease March hemoglobinuria Hypersplenism Paroxysmal nocturnal hemoglobinuria (PNH) 19 Ahmed Alsolami <dr. elliptocytosis Metabolism defect: G6PD deficiency.com> . prosthetic valves. drugs. pyruvate kinase deficiency Hemoglobin defect: sickle cell anemia. industrial/domestic substances Infectious:  malaria. cold Ab type Alloimmune:    hemolytic transfusion reaction hemolytic disease of newborn bone marrow transplantation Drug induced Non-immune: Chemical/physical:  microangiopathy.solami@gmail.• Extravascular Hemolysis is due to: Abnormal RBCs  trapped in the reticuloendothelial system  destroyed by macrophages  Classification of hemolytic anemias: Hereditary Membrane defect: spherocytosis.

Inherited Hemolytic anemias  Hereditary spherocytosis (autosomal dominant): Abnormal RBC membrane  spherical shape & less deformable  destroyed in spleen Manifestations: • • • • • Fluctuating jaundice Splenomegaly Pigment gallstone: due to increased release of bilirubin from RBC breakdown Aplastic crisis: if infection with Parvovirus has occurred  switch off the hematopoiesis in bone marrow Megaloblastic crisis: due to folate deficiency as a result of increased hemolysis Laboratory findings: • CBC: o Spherocytosis o ↑reticulocyte count • • ↑serum bilirubin Osmotic fragility test 20 Ahmed Alsolami <dr.solami@gmail.com> .

α and β chains bind to form the normal adult hemoglobin (A type). Splenomegaly and hepatomegaly as a result of excessive RBC destruction.com> • . Plasma electrophoresis: to detect the type of hemoglobin. extramedullary hemopoiesis and later because of iron overload. α chains bind to the available β chains “normally”. liver cirrhosis and endocrinopathies (growth retardation. hypothyroidism and hypoparathyroidism) Hb A (α+ β) 0% Hb A2 (α+ δ) 4-10% Hb F (α+ γ) 90-96% • • • Laboratory findings: • CBC: o Severe microcytic hypochromic anemia o Increased reticulocytes o Basophilic stippling: blue dots with staining due to hemoglobin aggregations. In β thalassemia  decreased synthesis of β chain  the excess α chains precipitate in erythroblasts and in mature RBC causing severe ineffective erythropoiesis and abnormalities to RBC membrane  destroyed in the reticuloendothelial system The production of gamma γ chains helps to decrease the excess α chain aggregation.solami@gmail. delayed puberty. Infections Bone marrow overexpansion  bossing of head. Thalassemia  Beta Thalassemia major: Normally. DM. prominent malar eminence Multiple blood transfusion  iron overload  hemochromatosis  heart failure (major cause of death). 21 Ahmed Alsolami <dr. but the remaining of α bind to either : Delta (δ) chain  Hb A2 type Gamma(γ) chain  Hb F type Type Thalassemia major Clinical features: • • The anemia becomes apparent at 3-6 months after birth when the switch from γ to β chain should take place.

Type Thalassemia minor Hb A (α+ β) 80-95% Hb A2 (α+ δ) 4-8% Hb F (α+ γ) 1-5% Laboratory findings: • CBC: o Microcytic hypochromic picture o Increased RBC count o Mild anemia due to slight Hb decrease • Plasma electrophoresis: to detect the type of hemoglobin. If 3 genes are missing  Hb H disease  moderate anemia and splenomegaly If 4 genes are missing  α thalassemia major  can’t carry oxygen  Hydrops Fetalis (the baby die very shortly after birth and look pale. Plasma electrophoresis: to detect the type of hemoglobin. 22 Ahmed Alsolami <dr.com> .  Alpha Thalassemia: There are 4 genes encoding for α chain synthesis: • If 1 gene is missing  α thalassemia trait  asymptomatic • • • If 2 genes are missing  α thalassemia trait (also)  microcytic picture with no anemia. Beta Thalassemia trait (minor): Usually symptomless. edematous with enlarged liver and spleen) Laboratory findings: • • CBC: o microcytic picture.solami@gmail.

leading to the following consequences: U U 1. long term problems: fatigue. Liver  hepatomegaly . Sickle cell anemia:  The homozygous disease Substitution of valine for glutamic acid in the 6th position in the β chain of hemoglobin  abnormal Hb S  sickle shaped of RBC. Adults: aseptic necrosis of head of femur. Lungs  o increased pulmonary hypertension  heart failure o pulmonary infarction  chest pain . due to vascular stasis and local ischemia Penis  “Priapism”. More common in sickle cell trait Mesentery  acute abdominal pain . acidosis. these cells have abnormal charge on the surface  increased adherence to vessel wall  vaso-occlusive crisis (precipitated by hypoxia.com> . The RBCs become rigid and destroyed in the spleen  anemia  symptoms and signs of anemia 2. bossing of the head and prominent malar eminence (due to marrow overexpansion). Aplastic crisis: if infection with Parvovirus has occurred  switch off the hematopoiesis in bone marrow 4. It occurs in the following organs: U U • • • • • • • • • • Bone  Infants: “hand-foot syndrome” causing painful swelling. Retina  retinopathy and blindness Leg  non-healing ulcer around the ankle. CNS  sinus thrombosis  stroke . pigment stones. Spleen  early in life: there is splenomegaly. infections. 23 Ahmed Alsolami <dr. a state of persistent painful eriction 3. and repeated attacks of occlusion  infarction with acute pain.solami@gmail. dehydration or infection)  organ infarction + low grade fever. back or chest pain due to bone involvement Kidney  papillary necrosis  tubular concentration defect and gross hematuria. Laboratory findings: • • CBC: o Sickle sells and target cells o ↓ Hb Hb electrophoresis  No Hb A is detected !! and Hb F is variable . Late: spleen is shrunken and fibrotic due to infarctions  “Autosplenectomy”.

Direct enzyme assay during a crisis may give “false” normal level due to the higher enzyme level in the newly formed reticulocytes. due to minor infarcts causing papillary necrosis. it occurs in crises but there is no chronic state of hemolysis and no splenomegaly. Causing damage to the RBC membrane  intravascular hemolysis and hemoglobinuria.com> . Manifestations: Acute symptoms and signs of anemia. 2. quinine. Hb denaturation by oxidative stress  Hb precipitate  Heinz bodies  removed by spleen  “Bite cells” on blood film during a crisis. primaquine. sulphonamides) Beans (so called: Favism) Chronic hemolysis may only occur in severe deficiency. blood count is normal. the blood film shows contracted and fragmented cells “bite cells”. Direct enzyme assay after the acute phase reveals the low G6PD level. Sickle cell trait: This is a benign condition with no anemia and normal appearance of RBC on blood film. Oxidative stress occurs with: • • • • Infections Drugs (dapsone. Hematuria is the most common symptom. 24 Ahmed Alsolami <dr. During a crisis.  G6PD deficiency (X-Linked inheritance): ↓G6PD enzyme  ↓ formation of reduced glutathione (Hexose monophosphate shunt)  Decreased ability to handle oxidative stresses  1. The enzyme deficiency is detected by direct enzyme assay on RBC.solami@gmail. it is self limiting because the new reticulocyte are made with near normal enzyme levels. The Hb S varies from 25-45% of the total hemoglobin. Laboratory findings: • • • • Between crises.

IgM is the main immunoglobulin involved.solami@gmail.com> . +ve Coombs’ test with IgG and complements Autoimmune thrombocytopenia  Cold autoimmune hemolytic anemia In cold environment auto Ab attach to RBC and destroy them. There is a chronic minor hemolysis in normal body temperature. Findings of hemolysis).Acquired hemolytic anemia A) Immune mediated hemolytic anemia  Autoimmune hemolytic anemia  Warm autoimmune hemolytic anemia In warm environment auto Ab (usually IgG alone or with complement) attach to RBC and destroy them. Causes: • • • • • • Idiopathic Autoimmune diseases Lymphomas Chronic myeloid leukemia Carcinoma Drugs (methyldopa) Laboratory findings: • • • Evidence of hemolysis (Lab. 25 Ahmed Alsolami <dr.

headache. o Transfusion related acute lung injury. o Transmission of infections. o Non-hemolytic allergic reactions (febrile or non-febrile). due to HLA Abs. pyrexia and a fall in blood pressure which may cause shock  acute renal failure). 26 Ahmed Alsolami <dr. pain in the lumbar region. Immediate life-threatening reactions associated with massive intravascular hemolysis are usually due to ABO incompatibility. o Iron overload. flushing. caused by positive transfer of leucoagglutins donor plasma causing endothelial and epithelial injury. vomiting. in repeated transfusions over many years. rigours. • Other reactions: o Febrile reactions. If severe  anaphylactic shock. +ve Coombs’ test with complements only Monoclonal IgM Ab  Alloimmune hemolytic anemias:  Complications of blood transfusions: • Hemolytic transfusion reaction: may be immediate or delayed. due to hypersensitivity to donor plasma proteins.solami@gmail.Causes: • • • • Idiopathic Lymphomas Paroxysmal cold hemoglobinuria Infections (mycoplasma pneumoniae. o Circulatory overload. shortness of breath. The clinical features of a major hemolytic transfusion reaction include urticaria.com> . infectious mononucleosis) Laboratory findings: • • • Evidence of hemolysis (Lab. o Post-transfusion purpura. Findings of hemolysis). precordial pain. caused by Abs in the recipient (who was previously transfused or pregnant) against a platelet-specific antigen.

• • Arteriovanous malformations.  Red cell fragmentation syndromes: These arise through physical damage to red cells as follows: U U • Abnormal surfaces: o Prosthetic heart valves. Hemosiderinuria is a constant feature and can give rise to iron deficiency which may exacerbate the anemia. o Arterial grafts. o Malignant diseases  March hemoglobinuria: Caused by damage to red cells between the small bones of the feet. mesenteric and hepatic veins.B) Non-immune hemolytic anemias  Paroxysmal Nocturnal Hemoglobinuria (PNH): Acquired. clonal disorder of marrow stem cells in which the RBCs become vulnerable to lysis by complements. 27 Ahmed Alsolami <dr.solami@gmail. Microangiopathic hemolytic anemia: o Disseminated intravascular coagulation DIC (see page 44) o Thrombotic thrombocytopenic purpura TTP (see page 41) o Hemolytic uremic syndrome HUS. o Vasculitis.com> . usually during prolonged marching or running . Platelets and white cells may also be affected  thrombosis of large veins including portal. The blood film doesn't show fragments.

lead & arsine o Severe burns 28 Ahmed Alsolami <dr. or increased synthesis and release of thromboplastic substances  microangiopathic hemolytic anemia as in DIC (see page44) o Malarial direct intravascular hemolysis.com> . or by extravascular destruction of parasitized RBCs  Chemical and physical agents: these conditions cause acute hemolysis: o Certain drugs e.solami@gmail. dapson & salazopyrin in high doses o The high copper levels in Wilson's disease o Poisons e. Infections: can cause hemolysis in a variety of ways such as: o ↑oxidative stress  precipitate acute hemolytic crisis in G6PD deficiency o Cause widespread endothelial injury by toxins.g.g.

skin or testes).g. Down's syndrome.solami@gmail. thrombocytopenia) o Infiltration of organs (e. Helicobacter Pylori o Protozoa e.com> . Bloom's syndrome.g.g. meninges. Klinefelter's syndrome. anemia. liver. Epstein-Barr virus EBV. Hodgkin's and non-Hodgkin's lymphomas. • Inherited factors: o the risk is greatly increased in some genetic diseases e. HIV.g. Alkylating agents o Radiation • Infection: o Viruses e. Malaria 29 Ahmed Alsolami <dr. brain.g.g. • Environmental factors: o Chemicals e. lymph nodes. Benzene o Drugs e. o Chronic myeloid leukemia (CML) Risk Factors: As in most diseases it is the combination of genetic background and environmental influence that determines the risk of developing a malignancy. Types: • Acute o Acute lymphoblastic leukemia (ALL) . Human herpes virus 8 (HHV-8) o Bacteria e. spleen.g. Fanconi's anemia.Leukemia The leukemias are a group of disorders characterized by the accumulation of malignant white cells in the bone marrow and blood. B-cell or T-cell specific.e. Bcell CLL. o There is a weak familial tendency in some disease e. neutropenia.g. o Acute myeloid leukemia (AML) • Chronic o Chronic lymphoblastic leukemia (CLL) . B-cell or T-cell specific. AML. These abnormal cells cause symptoms because of: U U o Bone marrow failure (i.

lymphadenopathy. malaise. respiratory infections) o Thrombocytopenia (spontaneous bruises. Clinical features: • Bone marrow failure: o Anemia (pallor.Acute Leukemias Pathogenesis: Genetic damage that results in  • • • An increased rate of proliferation Reduced apoptosis Block in cellular differentiation These events together cause accumulation of blast cells. lethargy and dyspnea) o Neutropenia (fever.  Acute lymphoblastic leukemia (ALL): Most common in  Children (highest at 3-7 years) Pathogenesis: A proportion of cases are intiated by genetic mutations that occur during development in utero. feature of mouth. resulting in  o Bone marrow failure o Organ infiltration The diagnosis of acute leukemia requires more than 20% of blast cells in the blood or bone marrow. with a secondary event possibly precipitated by abnormal response of the immune system to infection in childhood. bleeding gums and menorrhagia) Organ infiltration (Tender bones. skin. moderate splenomegaly.solami@gmail. purpura. hepatomegaly and gum hypertrophy) • 30 Ahmed Alsolami <dr.com> . throat.

com> . To differentiate between AML & ALL : AML  The Auer rod. Laboratory findings: The general hematological and biochemical findings are similar to those seen in ALL. Clinical features: Resemble those of ALL. it is pathognomic of AML.Laboratory findings: • CBC: o Pancytopenia o circulating blast cells Bone marrow: o Hypercellular with >20% leukemic blasts Biochemistry: o ↑ serum uric acid o ↑ serum calcium o ↑ serum lactate dehydrogenase LDH Radiography: o Mediastinal mass (enlarged thymus or Mediastinal lymph nodes characteristic of T-ALL) Immunological  TdT surface marker • • • •  Acute myeloid leukemia (AML): Most common in  Adults Pathogenesis: The pathogenesis of AML includes number of translocations and mutations which dysregulate cell division.solami@gmail. ALL  TdT surface marker on blast cells in characteristic of ALL 31 Ahmed Alsolami <dr. an esinophilic needle-like inclusions in cytoplasm of blast cells.

dyspnea and tachycardia Symptoms due to platelet dysfunction such as bruising. with increased circulating basophils. normochromic anemia is usual o Platelet count may be increased o ↓↓ Neutrophil alkaline phosphatase (NAP) score • • • Bone marrow is hypercellular with predominance of granulocytic precursors Cytogenic analysis  Ph chromosome ↑↑Serum uric acid 32 Ahmed Alsolami <dr.g. U U U Clinical features: • • • • • • Symptoms related to hypermetabolism (e. Chronic myeloid leukemia (CML): It is a myeloproliferative stem cell disorder resulting in proliferation of all hematopoietic lineages. It is a translocation of genetic material between chromosome 9 & 22. U Pathogenesis: 95% of the patients have a chromosome abnormality known as Philadelphia (Ph) chromosome. anorexia or night sweats) Splenomegaly is almost always present and is frequently massive Features of anemia may include pallor. menorrhagia or hemorrhage Gout or renal impairment caused by hyperuricemia Rare symptoms include visual disturbances and priapism Laboratory findings: • CBC: o ↑↑ WBC o A complete spectrum of myeloid cells is seen in the peripheral blood.com> . there is an increased rate of myeloid cell production with normal cellular differentiation and bone marrow function. Thus. lassitude. epistaxis. neutrophil and basophil). but manifesting predominantly in the granulocytic series (esinophil. weight loss. o Normocytic.solami@gmail.

Symmetrical enlargement of cervical. Chronic lymphocytic leukemia (CLL): CLL is a clonal malignancy of B-lymphocytes (rarle T-lymphocytes). U Clinical features: • • • • Recurrent infections due to hypogammaglobulinemia and cellular immune disfunction. in which 70-99% are lymphocytes. Splenomegaly is common. possibly caused by autoimmunity. • • Bone marrow is infiltrated with lymphocytes ↓↓ serum immunoglobulins 33 Ahmed Alsolami <dr.com> . causing impairment of immunity. Features of anemia and thrombocytopenia.solami@gmail. bone marrow failure and organ infiltration. o Normocytic. normochromic anemia is present later stages. axillary or inguinal lymph nodes. And it is the most common variety od leukemia. U Pathogenesis: In the disease B-lymphocytes fail to form antibodies therefore increasing number of immuno-incompetent cells accumulate. Laboratory findings: • CBC: o ↑↑ WBC.

Clinical features: • Superficial lymphadenopathy. anorexia or cachexia. Occasionally. pruritus. which are large malignant lymphoid cells of B-cell origin. usually the cervical 60-70%. axillary 10-15% or inguinal lymph nodes 612% are involved. The histological hallmark of Hodgkin's lymphoma is the presence of Reed-Sternberg (RS) cells.Lymphomas Lymphomas are a group of diseases caused by malignant lymphocytes that accumulate in lymphoid tissues. painless rubbery enlargement of LN.solami@gmail. U U U U Pathogenesis: Some studies suggested that the RS cell is often derived from a B-cell with a defect in the immunoglobulin gene that prevents synthesis of full-length immunoglobulin. U Types: • • Hodgkin's lymphoma Non-Hodgkin's lymphoma  Hodgkin's lymphoma: Hodgkin's lymphoma is caused by malignant lymphocytes that accumulate in lymph nodes and cause the characteristic lymphadenopathy. fatigue. 34 Ahmed Alsolami <dr. night sweat. weight loss. Constitutional symptoms such as fever. U • • Mediastinal lymph nodes are commonly involved. which can be detected by CT scan only. they may spill over into blood (leukemic phase) or infiltrate extranodal organs.com> . The disease is typically localized initially to a single lymph node region and then spreads to the contiguous lymph nodes. Epstein-Barr virus genome has been detected in 50% or more of cases in Hodgkin tissue.

• ↑↑Serum LDH 35 Ahmed Alsolami <dr.solami@gmail. normocytic anemia is most common. o Esinophilia or neutrophilia in one-third of patients. o Lymphopenia is evident in the advanced disease. liver and other extranodal sites Laboratory findings: • CBC: o Normochromic. o ↑Erythrocyte sedimentation rate (ESR).com> .Clinical staging: • • • • Stage I  involvement of one lymph node area Stage II  involvement of 2 or more lymph nodal areas confined to one side of the diaphragm Stage III  involvement of lymph nodes above & below the diaphragm Stage IV  indicates adiffuse or disseminated disease in the bone marrow.

The GIT is the most commonly involved extranodal site after bone marrow. Liver and spleen are often enlarged and involvement of retroperitoneal or mesentric lymph nodes is frequent. o Neutropenia or thrombocytopenia in advanced disease with marrow involvement. The extranodal involvement is more common than in Hodgkin's lymphoma. U Clinical features: • • Superficial ymphadenopathy in one or more peripheral lymph node regions. 36 Ahmed Alsolami <dr. Constitutional symptoms such as fever. • • • • • ↑serum LDH ↑ serum uric acid may occur Lymph node biopsy is the definitive investigation Bone marrow aspiration  infiltration by lymphoid tissue.solami@gmail. and patients may present with acute abdominal symptoms. Cytopenia may also be autoimmune in origin. normochromic anemia is usual but autoimmune hemolytic anemia may also occur. and weight loss Anemia. Oropharyngeal involvement. o Lymphos cells may be detected in peripheral blood. These cells are B-lymphocytes (in 70%) or T-lymphocytes (in 30%). "Waldeyer's ring" of lymphoid tissue in the oropharynx is frequently involved and cause sore throat or noisy or obstructed breathing. Non-Hodgkin's lymphoma: In this disease. • • • Laboratory findings: • CBC: o Normocytic. there is malignant proliferation of lymphocytes. Chest X-ray & abdominal CT scan to see lymph node involvement. neutropenia and thrombocytopenia may be presenting features in patients with diffuse bone marrow disease.com> . night sweat.

U These abnormal stem cells have the tendency to transform into  acute myeloid leukemia U Clinical features: • Features of bone marrow failure: o Anemia (macrocytic non-megaloblastic) o Thrombocytopenia (e. or platelets. the bone marrow is partly or wholly replaced by a clone of multipotent stem cells that have a mutation preventing their differentiation into RBCs. the bone marrow is usually hypercellular or normocellular but the peripheral blood shows pancytopenia. ring sideroblasts. multinucleated erythroblasts and iron overload in macrophages of bone marrow) o Abnormal morphology of granulocyte precursors and megakaryocytes.g. As a result.g.com> . o Signs of ineffective erythropoiesis (e. easy bruising or bleeding) o Infections.solami@gmail.Myelodysplasia (Myelodysplastic Syndromes) In this syndrome. Laboratory findings: • CBC: o Pancytopenia o Macrocytic picture of RBCs o ↓ Reticulocyte count • Bone marrow studies: o Hypercellular with increased number of blast cells. WBCs. 37 Ahmed Alsolami <dr.

because all of the hemopoietic components are derived from a single multipotent stem cell.com> . Myelofibrosis These disorders are closely related to each other. Polycythemia rubra vera 2. Indeed. 38 Ahmed Alsolami <dr. Three disorders are included in this category: 1. granulocytic and megakaryocytic cells). transitional forms occur.solami@gmail. and in many patients a transformation from one disorder into another occurs during the course of the disease. Essential thrombocythemia 3.Myeloproliferative disorders This is a group of disorders characterized by abnormal proliferation of marrow stem cells of one or more of the hemopoietic components (erythroid.

g. Headache. Splenomegaly in 75% of cases. U Clinical features: • • • • Features of hyperviscosity (e. Polycythemia rubra vera: It is associated with excessive proliferation of erythroid. and peptic ulcer disease is resulting perhaps from histamine released as a result of increase in basophils. night sweats and fatigue) Pruritus characteristically after a hot bath. epistaxis and hypertension) Features of hypermetabolism (e. the most obvious clinical signs and symptoms are related to the absolute increase in RBC mass. neutrophilia and basophila are common o ↑Platelets • Bone marrow studies: o Hypercellular with prominent megakaryocytes o ↓Iron stores • • • • ↓Serum erythropoietin ↑NAP score ↑Uric acid ↑ Serum LDH 39 Ahmed Alsolami <dr. granulocytic and megakaryocytic elements.g.com> . is due to seeding of the spleen with the neoplastic marrow stem cells.solami@gmail. Gout (as a result of raised uric acid production).g. • • • Laboratory findings: • CBC: o ↑Hb o ↑RBC count & hematocrit value o ↑WBC count. dizziness. Although platelets and granulocytes are increased. dyspnea and blurred vision) Features of expanded blood volume (e. Hemorrhage or thrombosis either arterial or venous are frequent.

cysts. hydronephrosis. Erythromelalgia. carcinoma) Tumours (e.Causes of polycythemia: • Primary: o Polycythemia rubra vera o Familial (congenital) polycythemia • Secondary: o Caused by compensatory erythropoietin increase in:     High altitudes Pulmonary disease and alveolar hypoventilation Cardiovascular disease. cerebellar hemangioblastoma)  Essential thrombocythemia: It is associated with excessive proliferation of the megakaryocytic element and overproduction of platelets. U U Clinical features: • • • • Thrombosis of arterial or venous systems. Hemorrhage as a result of platelet dysfunction (acute or chronic). other causes of polycythemia should be roled out !! Renal disease (e. a burning sensation felt in the hands or feet and relieved by aspirin. uterine leiomyoma. or even splenic atrophy due to infarctions.solami@gmail. 40 Ahmed Alsolami <dr.g. hepatocellular carcinoma.g.com> . espicially congenital with cyanosis Heavy cigarette smoking o Caused by inappropriate erythropoietin increase in:   • Relative: o Dehydration o Plasma loss as in burns or enteropathy *For diagnosing polycythemia rubra vera. Splenomegaly in 40% os cases.

extramedullary hemopoiesis takes place (spleen. It tends to be disordered and inefficient leading to moderate to severe anemia and thrombocytopenia in addition to splenomegaly and hepatomegaly.com> . chronic myeloid leukemia and myelofibrosis. other causes of increased platelets have to be roled out !!  Myelofibrosis: There is an abnormal proliferation of megakaryocytes and overproduction of platelet-derived growth factor which stimulates fibroblasts resulting in bone marrow fibrosis. *For diagnosing essential thrombocythemia. liver and lymph nodes). U 41 Ahmed Alsolami <dr.solami@gmail. Thus. trauma or postoperative o Chronic iron deficiency o Chronic inflammatory process (rheumatoid arthritis.Laboratory findings: • CBC: o ↑Platelet count o Platelets are abnormal and large • Bone marrow is similar to that in polycythemia rubra vera but with excess of abnormal megakaryocytes. Causes of thrombocythemia: • Reactive: o Hemorrhage. ulcerative colitis) o Malignancy o Chronic infections o Post-splenectomy • Endogenous: o Essential thrombocythemia o Accompanying polycythemia vera.

fever and night sweats). abdominal discomfort. 10-20% of patients this diorder transform into  acute myeloid leukemia. pain or indigestion). U o Characteristic "tear-drop" shape of RBCs. Features of hypermetabolism (loss of weight.g.solami@gmail. Laboratory findings: • CBC: o Anemia o ↑WBC & platelets at the time of presentation. but decrease dramatically later on. reflecting the increased but ineffective turnover of hemopoietic cells. U o Platelets are giant and defective in function. anorexia.com> . Symptoms of anemia due to bone marrow failure. ↑NAP score ↑serum LDH. is the presence of nucleated RBCs and immature WBCs in peripheral blood. o Leukoerythrocytosis. and related symptoms (e. but trephine biopsy shows a fibrotic hypercellular bone marrow. U • • • Bone marrow is difficult to aspirate.Clinical features: • • • • Splenomegaly. 42 Ahmed Alsolami <dr.

↑ serum calcium 43 Ahmed Alsolami <dr. • • Recurrent infections. • • Laboratory findings: • CBC: o Macrocytic non-megaloblastic anemia o Neutropenia and thrombocytopenia in advanced cases o ↑erythrocyte sedimentation rate (ESR) • • • • Serum electrophoresis  paraproteins in serum or Bence Jhons proteins in urine Bone marrow show increased count of plasma cells usually > 20% Radiological investigations show skeletal lesions. dizzines. deafness and stupor) o Bleeding tendency due to interference with platelet function and coagulating factors.com> .Multiple myeloma It is a neoplastic proliferation of plasma cells that accumulate in bone marrow. pathologic fractures. and Hypercalcemia Neutropenia and severe suppression of normal immunoglobulin secretion  Recurrent infections Excessive paraprotein production  Hyperviscosity syndrome: o Visual disturbances o Neurologic problems (headache. carpal tunnel syndrome and diarrhea.solami@gmail. osteoporosis. & secrete a monoclonal immunoglobulin protein in the serum (paraproteins) and urine (Bence Jhons proteins). hypercalcemia and the toxic effect of Bence Jhons proteins on cells lining the tubules  Renal failure in 50% of cases Amyloidosis occurs in 5% of cases with features such as macroglossia. Pathogenesis and Clinical features: • • Extensive infiltration of bone marrow  bone marrow failure  anemia and neutropenia These plasma cells stimulate osteoclasts  bone resorption  bone pain (especially backache).

o Normal platelet count and tests of coagulation (PT. Defective coagulation  characterized by o Petechiae and other evidences of bleeding from very minor surface trauma are usually absent U o Massive hemorrhage may follow operative or dental procedures or severe trauma.com> . U U o Normal platelet count and tests of coagulation (PT.APTT) o Normal bleeding time 2. Vascular disorders  characterized by o Spontaneous appearance of petechiae and easy bruising in the skin and mucous membranes.solami@gmail. epistaxes. excessive bleeding from minor trauma and menorrhagia. Platelet deficiency (thrombocytopenia) or dysfunction  characterized by o Spontaneous appearance of petechiae and easy bruising in the skin and mucous membranes.Bleeding disorders Abnormal bleeding may result from: 1.APTT) o Bleeding time is always prolonged U 3. excessive bleeding from minor trauma and menorrhagia. epistaxes. Hemorrhage into areas of the body subject to trauma such as joints of the lower extremities is characteristic. U o PT. APTT or both are prolonged U o Normal bleeding time 44 Ahmed Alsolami <dr.

mucous membranes and internal organs. o Purpura associated with infections (bacterial. And can cause: • • • Recurrent epistaxes Recurrent GIT bleeding  iron deficiency anemia Pulmonary & cerebral arteriovenous malformations o Connective tissue disorders: In the Ehlers-Danlos syndrome there are hereditary collagen abnormalities.solami@gmail. bruising or both The standard screening tests are normal (bleeding time. o Senile purpura caused by atrophy of the supporting tissue of cutaneous blood vessels.com> . measles. resulting in:    Defective platelet aggregation  purpura Hyperextensibility of joints Hyperelastic friable skin  Acquired vascular disorders: o Simple easy bruising is a common benign disorder in healthy women especially those in the child-bearing age. bruising and mucosal hemorrhage o Long-term steroid therapy or Cushing's syndrome  defective vascular supportive tissue  Steroid purpura 45 Ahmed Alsolami <dr. PT. viral or rickettsial) as a result of vascular damage by the organism or immune complex deposition (e. In vitamin C deficiency  Defective collagen  Petechiae. Vascular bleeding disorders: The underlying abnormality is either in the vessels themselves or in the perivascular connective tissue. dengue fever or meningococcal septicemia) o Scurvy. U The bleeding is mainly in the skin  Petechiae.g. APTT)  Inherited vascular disorders: o Hereditary hemorrhagic telangiectasia (autosomal dominant): Dilated microvascular swellings (small red dots) develop in the skin.

chemicals. Failure of platelet production: o Selective megakaryocyte depression   Rare congenital defects Drugs. lymphoma) Multiple myeloma HIV infection 2. other viruses. then brief explanations for some causes will follow: U U 1. malaria Drug-induced & heparin Post-transfusional purpura Feto-maternal alloimmune thrombocytopenia o Thrombotic thrombocytopenic purpura o Disseminated intravascular coagulation (see page 51) 46 Ahmed Alsolami <dr. viral infections o Part of general bone marrow failure:           Cytotoxic drugs Radiotherapy Aplastic anemia Megaloblastic anemia Myelodysplasia Myelofibrosis Leukemia Marrow infiltration (e. carcinoma. Increased consumption of platelets: o Immune  Autoimmune • •     Idiopathic thrombocytopenic purpura Associated with SLE. Thrombocytopenia: These are the causes of thrombocytopenia.solami@gmail.com> .g. CLL or lymphoma Infections: HIV.

Dilutional loss (massive transfusion of stored blood to bleeding patient) • Autoimmune (Idiopathic) thrombocytopenic purpura (ITP): It may be divided into Chronic and Acute forms.com> . Chronic Idiopathic thrombocytopenic purpura: Antibodies against platelets (usually IgG)  premature removal of platelets from the circulation by macrophages of the reticuloendothelial system. Abnormal distribution of platelet (splenomegaly) 4. The onset is insidious with petechiae. infection with HIV. especially the spleen. Most cases are caused by non-specific immune complex attachment.solami@gmail. U U It is usually idiopathic but may be associated with SLE. Laboratory findings: o ↓ Platelet count as low as 10-50 × 109/L o Normal hemoglobin concentration and WBC count o Bone marrow  normal or increased number of megakaryocytes o Demonstration of specific antiglycoprotein antibodies on the platelet surface b. Acute Idiopathic thrombocytopenic purpura: In 75% of patients the episode follows vaccination or an infection such as chickenpox or infectious mononucleosis. chronic lymphocytic leukemia (CLL).3. 47 Ahmed Alsolami <dr. Spontaneous remissions are usual but in 10-15% of cases the disease becomes chronic. easy bruising and menorrhagia. Hodgkin's lymphoma or autoimmune hemolytic anemia. a.

com> . 48 Ahmed Alsolami <dr. It often occurs 10 days after blood transfusion. "pentad" of TTP: o Thrombocytopenia  bleeding tendency o Microangiopathic hemolytic anemia due to the narrowing of the blood vessels by the thrombi o Neurologic abnormalities o Renal failure o Fever • Abnormal distribution of platelet (splenomegaly) Thrombocytopenia which occur with splenomegaly is due to "pooling" of more than 90% of the platelets by the spleen. connective tissue disease. stem cell transplantation or cardiac surgery  production of inhibitory IgG autoantibodies  block the enzyme action Clinical features.• Post-transfusion purpura: It is due to the development of antibodies against platelets in the received blood.solami@gmail. autoimmune. drugs. • Thrombotic thrombocytopenic purpura (TTP): There is deficiency of the enzyme that breaks down ultra large Von Willebrand factor ULVWF(the most adhesive and reactive form of Von Willebrand factor)  ULVWF attach to the endothelial cells  adherence of the passing platelets  formation of large occlusive thrombi  embolising to microvessels downstream  organ ischemia TTP occurs in 2 forms: o Familial: the enzyme that breaks down ULVWF is nonfunctional due to multiple mutations o Acquired: infection.

muscles hematomas. 49 Ahmed Alsolami <dr. clopidogrel. alcohol and radiographic contrast)  Coagulation disorders:  Hereditary coagulation disorders • Hemophilia A (sex-linked): The defect is an absence or low levels of plasma factor VIII due to a mutation in the encoding gene on the X chromosome. Platelet dysfunction:  Hereditary disorders: • • • Thrombasthenia Bernard-Soulier syndrome Storage pool diseases  Acquired disorders: • • • • • Antiplatelet drugs (e.solami@gmail. tirofiban) Hyperglobulinemia (as in multiple myeloma and Waldenstrom's disease) Myeloproliferative and myelodysplastic disorders Uremia Others (heparin. dipyridamole.com> . abciximab. Clinical features: o Excessive bleeding into joints (hemarthrosis). aspirin.g. mucous membranes and internal organs (brain. kidney. eptifibatide. dextrans. hepatitis C or B infection. patients may show symptoms and signs of transmitted disease through infected blood such as HIV. GIT) o Operative and post-traumatic hemorrhage are lifethreatening o Because of the continuous need to blood transfusion.

and factor VIII-VWF binding assay is performed. Laboratory findings: o VWF level is usually low o Factor VIII level is often low. o APTT may be prolonged o Platelet count is normal 50 Ahmed Alsolami <dr.Laboratory findings: o Abnormal activated partial thromboplastin time (APTT) o Abnormal factor VIII clotting assay o Normal bleeding time and PT tests • Factor IX deficiency (sex-linked): Also called Christmas disease or hemophilia B.solami@gmail.com> . The two disorders can only by distinguished by specific coagulation factor assay. Gene mutation  either reduced level or abnormal function of VWF  decreased level of factor VIII and platelet adhesion  increased bleeding tendency mostly from mucous membranes and superficial cuts and operative and post-traumatic hemorrhage. shows identical clinical features to those of hemophilia A. Laboratory findings: o Abnormal APTT o Abnormal factor IX clotting assay o Normal bleeding time and PT tests • Von Willebrand disease (autosomal dominant): Von Willebrand factor (VWF) promotes platelet adhesion to damaged endothelium & it is the carrier molecule for factor VIII.

g. defibrinating agents or thrombolytics Massive transfusion syndrome • Disseminated intravascular coagulation (DIC): Pathogenesis: 2 major mechanisms may trigger DIC: 1. from gram-negative and grampositive sepsis "endotoxins" or "exotoxins")  initiation of the intrinsic coagulation pathway. RA) Therapy with heparin.g. 51 Ahmed Alsolami <dr.com> . from the placenta in obstetric complications. by temperature extremes as in heat stroke or burns. Acquired coagulation disorders: Causes: o Deficiency of vitamin K as in:     Biliary obstruction Malabsorption of vitamin K (e. tropical sprue. carcinoma and neoplastic cells.g. antibodies against factor VIII) Non-specific inhibitors (e. by deposition of Ag-Ab complexes as in SLE. warfarin) Hemorrhagic disease of the new born o Deficiency of clotting factors due to:   Liver disease Disseminated intravascular coagulation o Inhibition of coagulation:     Specific inhibitors (e.g.g. from leukemic cells. Release of tissue factor (factor VIIa) or thromboplastic substances into the circulation (e. antibodies found in SLE. gluten enteropathy) Vitamin K-antagonist therapy (e. 2.g.solami@gmail. by gram-negative sepsis "endotoxins")  exposure of collagen in the endothelial matrix  initiation of the extrinsic coagulation pathway. Widespread injury to endothelial cells (e.

and microangiopathic hemolytic anemia as RBCs are traumatized while passing through the fibrin strands. o Bleeding tendency as platelets and clotting factors are consumed and there is a secondary release of plasminogen activators Laboratory findings: o ↓ platelet count o ↓ fibrinogen concentration o PT and APTT are prolonged in the acute syndromes o Blood film shows RBC fragmentation as a result of microangiopathic hemolytic anemia 52 Ahmed Alsolami <dr.com> .solami@gmail.Clinical features: DIC has 2 consequences: o Widespread fibrin deposition within the microcirculation  organ ischemia due to vascular occlusion.

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