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Anemia
Normocytic Microcytic Macrocytic Hemolytic
Reticulocyte Index
 Acute Blood loss  Iron-deficiency  B12, Folate deficiency ↑ ↓
 Hemolysis  Thalasemia  Sideroblastic
 Sideroblastic  Mylodysplastic syndrome
 Chronic disease (MDS)
 Hypothyroidism
 Alcoholism
Blood loss  iron-deficiency anemia   Liver disease
microcytosis  Drugs:
o Azathioprine
TICS
o 6-mercaptuprine
MD o Hydroxyurea
α –thalasemia (3 Gen deleted) 
FLASH o Phenytoin
↑ Reticulocytes
o Zidovudine

↓ Hematocrit ↓ MCV (X < 80) ↑ MCV

↑ Reticulocytes
↓ Reticulocyte count ↓ Reticulocyte count

Iron:
 Need:
o Normally Needed  1-2 mg/d
o Menstruating Women  2-3 mg/d
o Pregnancy  5-6 mg/d Transfusion (Packed RBC):
 Absorption: Duodenum  4 mg/d  Symptomatic
o ↑ vitamin D o Dyspnea
o ↓ Tea, IBD, Celiac disease o Confusion
 Storage: o Syncope
o Ferritin o ↓BP, ↑HR
o Hemosiderin o Chest pain
 Transfer:  ↓↓ Hematocrit in Elderly or Heart disease (25-30%)
o Transferrin
 Tests:
o Bone marrow aspirate  Gold standard for Iron Stores
o Serum ferritin  Blood test for Iron Stores
Fresh Frozen Plasma: (FFP)
 Replace clotting factors in patient with:
o ↑ Prothrombin Time (PT)
o ↑ activated partial thromboplastin time (aPTT)
o ↑INR
o Bleeding
o NOT FOR Hemophilia A,B or Von-willebrand disease

Cryoprecipitate:
 Replace fibrinogen
 Provide ↑ amounts of clotting factors in small plasma volume
 ↑VWF, ↑ Factor 8

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Anemia (Microcytic)
Iron Deficiency Sideroblastic Anemia

Et: Plummer-Vinson-Syndrome: ET:

 ↑ demand (Pregnancy)  Dysphagia  X-linked
 ↓ Supply:  Glossitis  Defect in Heme Biosynthesis
o Cow’s milk  Iron deficiency anemia  Drugs:
o Tea  Isoniazid
o Post-gastrectomy  Chloramphenicol
o Malabsorption ( IBD, Celiac disease, atrophic gastritis)
 Alcohol ( suppress Bone marrow)
 ↑ Loss:
 Lead poisoning
o Menorrhagia
 Zink toxicity
o Uterine Bleeding
 Vitamin B6 deficiency
o Peptic ulcer
S+S:
o Hemolysis
 Anemia symptoms
S+S:
 Fatigue, weakness, dizziness  Hepatosplenomegaly
 Irritability, confusion, Exercise intolerance  Fe2+-overload syndrome
 Syncope, Dyspnea Dx:
 Feeling cold, ↓ concentration  ↓ MCV
 Nail change  koilonychias (spoon shaped)  ↓ MCV  ↑ Iron (serum)
 Pica (appetite for non-food  ice, dirt)
 ↑ Iron (serum)  ↑ Ferritin
↓MCV ↑RDW  ↑ Ferritin
Dx:
↓Iron ↑ Platelet count  Prussian Blue  ringed sideroblasts (most accurate)
 ↓ Iron (serum)
 ↓ Ferritin
↓Ferritin  Bone marrow Biopsy  Ringed sideroblasts (diagnostic hallmark)
Tx:
 ↓ MCV
 Vitamine B6 (pyrodixine) Replacement
 ↑ TIBC (Total iron binding capacity)  a lot of open sites on
Transferrin.  Treat the cause
 ↑ RDW (red cell distribution of width)
 ↑ Platelet count
 Bone marrow Biopsy  Most accurate (↓ Iron) Thalassemia
Tx:
 Oral ferrous sulfate (IM if insufficient, or can’t absorb) Def:
 defects in production of the a or ß chains of hemoglobin
 resulting imbalance in globin chains leads to ineffective erythropoiesis
Chronic Disease and hemolysis in the spleen or BM
 increasing severity with increasing number of alleles involved.

Def:
 Impaired iron utilization α-Thalasemia β-Thalasemia
 Trapping of Iron in macrophages, Ferritin
1 Gene
 The peptide hepcidin is felt to be the main mediator of the effect Normal ↑ Hb-F, ↑ Hb A2
deleted
Et:
 Infection, malignancy, inflammatory and rheumatological disease. 2 Gene mild anemia, normal
 Chronic Renal disease deleted electrophoresis
 Chronic Liver disease moderate anemaia.
 Endocrine (DM, ↓ Hypothyroidism, ↓Hypogonadism) 3 gene ↑ Reticulocytes
Dx: deleted Hemoglobin H
 ↑ acute phase reactants ( ESR, CRP, Fibrinogen) Hemolysis
 ↑ Ferritin (or normal) 4 gene
 ↓MCV Death in Utero
↓MCV ↑ Ferritin deleted
 ↓HB (No synthesis)
↓HB (No synthesis) ↑CRP, ESR
 ↓ Iron (Trapped)
↓ Iron (Trapped) Dx:
 ↓ TIBC
↓ TIBC  α-Thalasemia  Genetic Study (most accurate)
 ↓ reticulocytes
↓ reticulocytes o 3-genes deleted  ↑ Reticulocytes, Hemoglobin H
Tx:  β-Thalasemia  Hb electrophoresis
 Treat underlying disease
 Erythropoietin (in chronic renal failure) Tx:
 β-Thalasemia (major)  chronic Transfusion lifelong
Iron Deficiency Chronic disease  Iron overload  iron chilator (Deferoxamine)
Iron ↓ ↓  1 deleted Gen  no treatment
TIBC ↑ ↓
Ferritin ↓ ↑/Normal

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Anemia
Vitamin B12 / Folate deficiency (Macrocytic)

Def:
 Vitamin B12:
o Binds to intrinsic factor secreted by gastric parietal cells
o Absorbed in terminal ileum

Et:

Vitamin B12 Folate

 Pernicious anemia  Diet (Goat’s milk  No Folate)

 Pancreatic Insufficiency   elderly
enzymes needed to absorb  Psoriasis
Vitamin B12  ↓ Green vegetables
 Diet (vegetarian)  Drugs:
 Crohn disease o Phenytoin
 Celiac disease o Sulfa
 Terminal ileum Problems
 Gastrectomy
 Post-surgical
 Worm (latum)

S+S:
 Neurological: ( confusion, delirium, dementia)  reversible
 Cord (irreversible):
o ↓vibration sense
o Spastic weakness
o Hyperactive reflexes
o ataxia
 Peripheral neuropathy (most common)

Dx:
 Megaloblastic anemia
 ↓ reticulocytes
 ↑LDH, ↑ Indirect Bilirubin, ↑ Hypercellular Bone marrow
 ↑Homocysteine
 ↑MCV
 Macroovalocytes
 Hypersegmented Neutrophiles (not seen in alcohol abuse) 
 ↑ Methyl malonic acid (only in Vitamin B12)
 Pernicious Anemia  confirmed with:
o Anti-intrinsic factor
o Anti-parietal cell antibodies

Tx:
 Replacement  Vitamin B12, Folate (complication  Hypokalemia↓)

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Aplastic anemia ( Normocytic) Normochromic Anemia

Def: Normal MCV  check  Reticulocytes Index:

 destruction of hematopoietic cells of the bone marrow leading to  ↓ Low (X< 2%) Aplastic anemia
pancytopenia and hypocellular bone marrow ↓.
 ↑high (x > 2-3%) 
Et:
o Hemolysis
 Congenital:
o Fanconi’s Anemia o Acute Blood loss
o Schwachman-Diamond-Syndrome (Bone marrow failure +
Pancreatic Insufficiency). Hemolytic Anemia
 Infection (HIV, HBV)
 Drugs:
Types:
o Chemotherapy
 Spherocytosis
o Radiation
 Pyruvate-kinase-deficiency
o Chloramphenicol  G6PD-deficiency
S+S:  Thalasemia
 Anemia  Hemoglobinopathie
 Thrombocytopenia  Transfusion reaction
 Pancytopenia  Microangiopathic
Dx: Dx:
 Anemia OR Neutropenia OR Thrombocytopenia +/- Pancytopenia  ↓Htk
 ↓Haproglobin
 Bone marrow :
 ↑LDH
o Aplasia/ Hypoplasia + Fat Replacement  ↑Indirect Bilirubin
o ↓Cellularity  ↑Reticulocytes
Tx:
 Transfusion (RBC + Platelet) Sickle cell disease

Def:
Autoimmune Hemolysis
 Chronic hemolytic anemia with alwayyyys ↑ Reticulocytes
 autosomal-recessive
 mutation of hemoglobin (the β chain has glu  val).
IgG (Warm) IgM (Cold)
Et:
CLL CLL 
Et SLE Mycoplasma pneumoniae S+S:
Drugs: phenytoin, Penicillin EBV  PAINFUL
Coombs Test  IgG abtibody Symptoms Nose, ears, fingers  Hemolytic anemia
Dx Cold agglutinin Titer  most accurate  Jaundice
Microspherocytosis
 Bilirubin Gallstones  ↑ Bilirubin
Glucocorticoides  best initial Warming  Autosplenectomy  + Infection (encapsulated)
Tx (IgGGGG  Glucocorticosteroids) Rituximab  Osteomyelitis ( from salmonella)
Splenectomy  recurrent  Retinopathy
Rituximab **  Stroke
 Skin ulcer
 Dactylitis (children)
Glucose 6 phosphat-dehydrogenase Deficiency (G6PD)  Avascular necrosis  femoral head
 Vasoocclusive crisis  infarction
Def: Dx:
 Deficiency in G6PD  + RBC sensitivity to oxidative stress (lack of  Peripheral smear  best initial
reduced Glutathion).  Hb-electrophoresis  most accurate
 X-linked recessive (only MEN)  Howell-jolly-bodies
Tx:
Et:
 O2, Hydration, Analgesics
 Infection (oxidant stress)  AB (Ceftriaxone, Moxifloxacin) - if FEVER, ↑WBC
 Fava beans  Folic acid
 Drugs: Sulfonamide, antimalarial,  Vaccination (Pneumococcal)  because of Autosplenectomy
S+S:  Hydroxyurea (increases HbF)
 Mediterranean  sudden Anemia + Jaundice
 Normal sized spleen (No splenomegaly)
Dx:
 Heinz bodies  best initial
 G6PD-level  most accurate (after 2 months)
Tx:
 avoid oxidant stress  if severe  Transfusion

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Hereditary Spherocytosis

Def:
 Autosomal dominant
 Defect in the membran of the red cell leading to abnormal round shape
and loss of normal flexibility.

S+S:
 Hemolysis (recurrent), or Family history
 Jaundice
 Splenomegaly
 Bilirubin Gallstones

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Pulmonary Edema Pulmonary Hypertension

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Pulmonary Edema Pulmonary Hypertension

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Platelet Bleeding Factor Bleeding

Primary Secondary

Inability to form an adequate platelet

plug due to:
 Blood vessel disorder
 Platelet disorder:
o Abnormal function
o Abnormal Nr. (thrombocytopenia)
 vWF disorder

Superficial Deep

Epistaxis Joints
Genigival Muscles
Purpura GIT
Mucosal surfaces (gum) Hematoma
Vaginal Bleeding Hemarthroses
Petechiae
Ecchymosis

ITP Hemophilia A
HIT Hemophilia B
TTP/HUS Vitamin K deficiency
vWF DIC

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Shape Association
Hereditary spherocytosis
Spherocytes
Immune hemolytic anemia
Microangiopathic hemolytic anemia
Helmet cells ( HUS,TTP,DIC)
Prosthetic Valve

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Primary Hemostasis Disorders

Immune Thrombocytopenic Purpura (ITP) Heparin – Induced Thrombocytopenia (HIT)

Def: Def:
 Most common cause of isolated Thrombocytopenia (Platelet < 100,000)  Heparin Treatment  immune mediated reaction  + coagulation
 Anti-platelet antibody bind to platelet surface  ↑ splenic destruction activation.
 Impaired platelet production  ↑incidence with unfractionated heparin
S+S:  presents 5 to 10 days after the start of heparin with a marked drop in
platelet count(more than 30%)
 Asymptomatic

 Minimal bruising  severe Bruising
Dx: S+S:
 Isolated thrombocytopenia (normal Htk, normal WBC)  Venous Thrombosis: DVT, PE, Limb gangrene, cerebral sinus thrombosis
 Normal aPTT, PT  Arterial Thrombosis: MI, Stroke, Organ infarct (kidney, mesenteric)
 Biopsy (Bone marrow)  ↑ Megakaryocytes  Acute inflammatory reaction: Fever, chills, Flushing

Tx: Dx: Thrombosis

 If Platelets > 30,000  NO Treatment  Serotonin release assay.
No Bleeding
 ELISA for platelet factor 4 (PF4) antibodies
 Emergency (active Bleeding, CNS,GIT bleeding):
o Corticosteroides (Prednisone) Tx:
o IVIG (if severe)  STOP Heparin
o Anti-D (if severe)  Administer direct Thrombin inhibitors:
o Platelet transfusion o Argatroban
o Splenectomy (if recurrent) o Lepirudin Never ever Transfer Platelets
 Before Splenectomy give Vaccination: o Bivalirudin  worse the situation
o fondaparinux
 Pneumococcal
 H.influenza
 N.meningitides
o Retuximab

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Pulmonary Edema Pulmonary Hypertension

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Pulmonary Edema Pulmonary Hypertension

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