By Ashok Vinoodhini Keziah Sharmita Hidayah Sreeram Paula Kenny

Major Component of Hemostasis: 1. Vascular component Primary Hemostasis 2. Platelet component 3. Coagulation component Secondary Hemostasis
Defect can be: • Quantitative (deficiency) • Qualitative (functional)

Primary Hemostasis Platelet Disorder Quantitative (deficiency)

Secondary Hemostasis

Vascular Defects Qualitative (functional)

Coagulation Disorders
Congenital Acquired

Congenital Acquired

Disorders of Primary Hemostasis .

Thrombocytopenia • Defined as a reduction in the peripheral blood platelet count below the normal limit of 1.5x 104 /micro liter • Confirmation by Blood film .

usually of autoimmune or infectious origin • TAR Syndrome: – radial aplasia or hypoplasia and thrombocytopenia • Wiscott Aldrich Syndrome: – an X-linked recessive disease characterised by thrombocytopenia. eczema. lymphopenia and depressed cellular immunity. .Thrombocytopenia (Congenital) • Megakaryocytic hypoplasia: – underdevelopment of megakaryocytes which normally develop in bone marrow and fragment to produce platelets . malignant lymphoma.

Infection.Thrombocytopenia ( Acquired) 1. Radiation and chemotherapy. Decreased platelet production • Bone marrow Failure. Others • Drug-Induced. Sepsis-related . Alcohol 2. TTP 3. Increased platelet destruction • ITP. Myelodysplasia. Folate or B12 deficiency. Marrow infiltration. Increased platelet sequestration • Hypersplenism 4.


Platelet Dysfunction (Congenital) • Glanzman’s Disease: – platelets contain defective or low levels of glycoprotein IIb/IIIa (GpIIb/IIIa). which is a receptor for fibrinogen • Bernard Soulier Syndrome: – absence of a platelet membrane glycoprotein (platelet membrane von Willebrand factor) leading to defective platelet adhesion .

Platelet Dysfunction (Acquired) • Drugs : Aspirin • Uremia • Multiple Myeloma .

Idiopathic Thrombocytic Purpura (ITP) by Keziah Tan .

Immune thrombocytopenic purpura (ITP): • Thrombocytopenia is due to immune destruction of platelets. • The antibody-coated platelets are removed following binding to Fc receptors on macrophages.

ITP in Adults
• More chronic than in children. • Characteristically seen in women and may be associated with other autoimmune disorders such as SLE, thyroid disease and autoimmune haemolytic anaemia (Evans’ syndrome). • Also seen in patients with chronic lymphocytic leukaemia and solid tumours, and HIV. • Platelet antibodies are detected in about 60– 70% of patients, the antibodies often have specificity for platelet membrane glycoproteins IIb/IIIa and/or Ib.

Clinical Features
• Major haemorrhage is rare and only occur in severe thrombocytopenia. • Purpura and spontaneous bruising are characteristic, but there may also be oral, nasal, GIT or genitourinary bleeding. (Bleeding gums, epistaxis & menorrhagia) • Spontaneous bleeding usually occur when platelet count <20 × 109/L. • Severe thrombocytopenia (<10 × 109/L) may result in retinal haemorrhage and potentially fatal intracranial bleeding. • Physical examination is normal except for evidence of bleeding. Splenomegaly is rare.


Investigations • Blood film is the most useful initial investigation. • Examination of the bone marrow may reveal increased megakaryocytes in consumptive causes of thrombocytopenia. hypoplastic anaemia or myelodysplasia. or the underlying cause of bone marrow failure in leukaemia. .

• Platelet transfusion is rarely required and is usually confined to patients with – bone marrow failure and platelet counts < 10 × 109/L. or – clinical situations with actual or predicted serious haemorrhage. • Patients with platelet counts >30 × 109/L or without spontaneous bruising or bleeding generally require no treatment. (intracranial or extreme haemorrhage) .Treatments • Treatment (if required) depends on the underlying cause.

– Patients who fail to respond to corticosteroids or require high doses to maintain a safe platelet count should be considered for splenectomy. . • IV immunoglobulin (IV IgG) – Responses are only transient (3–4 weeks) with little lasting effect.Treatments First-line therapy • Oral corticosteroids 1 mg/kg. – very useful in rapid rise in platelet count. especially before surgery.

Second-line therapy Splenectomy • responsive in majority of patients. two-thirds will achieve a normal platelet count. • Patients who do not have a complete response can still expect some improvement. .

Third-line therapy In fail splenectomy: • Highdose corticosteroids. vinca alkaloids. • Specific immunomodulatory monoclonal antibodies: rituximab. • Thrombopoietin receptor agonists (eltrombopag and romiplostim) – for long-term use & refractory ITP. combination chemotherapy. danazol. immunosuppressive agents such as azathioprine. Rh0(D) immune globulin (anti-D). . mycophenolate mofetil. IV IgG. ciclosporin and dapsone.

Disorders of Secondary Hemostasis .

General Overview Bleeding Disorders Cougulation disorders Inherited Acquired DIC Liver disease Vitamin K deficiency Platelets Disorders Qualitative Quantitative Inherited Acquired Thrombocytosis Haemophilia Von willebrand disease Thrombocytopenia 22 .

Inherited Bleeding Disorders Nur Hidayah Binti Rosli Sharmita a/p Kokulabalan 23 .

Hemophilia  A group of blood disorders in which there is defect in clotting factors  70% are X-linked recessive disorder.  Types : A:Deficiency in factor VIII (Classic hemophilia) B: Deficiency in factor IX (Christmas disease) C: Deficiency in factor XI 24 . 30% spontaneous mutation.

000 male births.Hemophilia A  Occur in approximately 1 in 5.  Hemophilia A is approximately 5 times more common than Hemophilia B. .

26 .

Clinical Features 27 .

 The bleeding tendency in hemophilia is determined in large part by the baseline level of the deficient or defective clotting factor. 28 . The clinical symptoms and signs of Hemophilia A and B are identical.

Classification Severe (<1% of normal) Clinical Features  Spontaneous bleeding occurs multiple times each year. but excessive and prolonged bleeding can occur with trauma and invasive surgical or dental procedure.<40% of normal) . 29 Moderate (1-5% of normal) Mild (>5% .  Excessive bleeding is usually only documented with trauma or invasive procedures.  Spontaneous bleeding is infrequent.

 Eventually. the joints become painful and less mobile.Hemarthrosis  In severe hemophilia.  With repeated episodes of bleeding. the development of hemarthrosis (bleeding into a joint) is a classical clinical sign. this can result in immobility and muscle wasting of the affected limb 30 .

After a lifelong experience of multiple hemarthrosis. the patient has very limited mobility. and his leg muscles are markedly atrophic because of a lack of use. His ankles and knees show deformities. 31 .Chronic Atropathy A 55-year-old patient with severe hemophilia A who is a wheelchair user.

thus causing compression of adjacent organs. compromise of the airway.. and nerves and. retroperitoneal bleeds or hematomas of the neck) may cause extensive blood loss and be life or organ threatening because of their propensity to expand.  In moderate and severe hemophilia. blood vessels.g. soft tissue hematomas often undergo progressive enlargement and may need to be treated.  Some soft tissue bleeds (e. 32 . in the case of neck hematomas.Soft Tissue Hemorrhages  Superficial hematomas (bruises) may resolve spontaneously without the need for treatment.

Other Clinical features       Illiapsoas bleeding Joint Swelling Easy bruising Epistaxis Haematuria Intracranial hemorrhage 33 .

Investigations  Hemophilia A is diagnosed by testing the level of factor VIII coagulation activity in the blood. 34 .  Prenatal diagnosis can be done at 9 to 11 weeks by chorionic villus sampling (CVS) or by fetal blood sampling at a later stage 18 or more weeks.

Investigations Investigations Result Activated partial thromboplastin time (aPTT) Prolonged Protrombin time (PT) Bleeding time Factor VIII vWF Normal Normal Reduced Normal 35 .

36 .Management  Recombinant factor VIII concentrate IV infusion. ** Aspirin and NSAIDs drugs should be avoided in all patient with Hemophilia. It stimulates endogenous release of factor VIII and vWF.  Desmopressin (DDAVP) can be given in patient with mild hemophilia. highly purified virally inactivated plasma derived product should be used.  If not available.

May be difficult to cannulate  Central venous access devices may become infected or thrombosed 37 .transmitted infections  Hepatitis A. B and C  HIC  Vascular access  Peripheral vein.Complications of Treatment  Inhibitors/Antibody development  Reduce the effect of treatment  Require the use of very high doses of factor VIII for treating bleeding  Transfusion.

Hemophilia B 38 .

Hemophilia B  Also known as Christmas Disease  Factor IX deficiency  Incidence is 1 in 30.000 male births  Inheritance and clinical features identical to Hemophilia A  Treatment – Factor IX concentrates. 39 .

Hemophilia C 40 .

Haemophilia C  Mild bleeding tendency.  Autosomal recessive disorder 41 .  Hemophilia C is much more rare.

Von Willebrand’s Disease 42 .

43 . a Finnish physician.  The disease was first described by Erik von Willebrand.(vWF)  The disease is estimated to occur in 1% to 2% of the population.Introduction  Caused by a defect or deficiency of von Willebrand Factor.

44 .Normal Function  vWF mediates the binding of glycoprotein Ib (GPIb) to collagen.  This binding helps mediate the activation of platelets and formation of primary hemostasis  vWF also plays a role in stabilizing factor VIII C in plasma.

 Mild to moderately severe bleeding.  70-80% of cases.  Desmopressin is the treatment of choice.Classifications Classified into 3 types : Type I  Autosomal Dominant. 45 . vWF activity and vWF antigen may be reduced concordantly or near-normal.  FVIII.  Partial quantitative deficiency of vWF. All multimers present and in same relative proportion. but reduced.

• Desmopressin is not useful. normal FVIII. • • • • 46 . vWF containing concentrate is the treatment of choice.Type 2 : Qualitative abnormality of vWF and may have normal levels of vWF. Type 2A Autosomal Dominant 10-15% vWD cases. normal vWF antigen. decreased large multimers on electrophoresis. Due to defective plt-vWF interaction Low vWF activity. • Humate-P.

Type 2B • Autosomal Dominant • 5% cases. leading to a mild thrombocytopenia. • vWF activity less than vWF antigen. vWF containing concentrate is the treatment of choice. • Humate-P. 47 . • There is increased platelet-vWF interaction due to increased affinity of vWF for GPIb • Increased binding of large multimers to platelets results in loss from circulation. • DDAVP is contraindicated as it may exacerbate thrombocytopenia.

Reduced binding of vWF to GPIb. Rare. Reduced vWF activity. • • • • 48 . • Humate-P. FVIII reduced. full spectrum of vWF multimers (differentiating this from type 2A). vWF concentrates is the treatment of choice.Type 2M Autosomal dominant. variable vWF antigen.

bleeding is associated with the deficiency of FVIII and the bleeding presentation is that of hemophilia.Type 2N Autosomal recessive. antigen. Rare. Defective interaction with FVIII. • Humate-P. • Normal vWF activity. • • • • 49 . Thus. vWF containing concentrate is the treatment of choice. RIPA and multimer patterns but FVIII is reduced. Sort of an autosomal hemophilia A.

joint. • Markedly reduced or no expression of vWF mRNA. mucous surfaces. • Humate-P.Type 3 • Rare. soft tissue. oral cavity. • Severe bleeding involving skin. 50 . • Characterized by marked decrease if not absence of detectable vWF. vWF concentrates and Desmopressin may be needed for management.

Clinical features       Mucocutaneous bleeding Epistaxis Gingival bleeding Cutaneous bruising Menorrhagia In severe cases where there is Factor 8 deficiency. patients may have manifestations similar to Hemophilia A ( Hemarthrosis ) 51 .

 vWF antigen • plasma vWF antigen measured by ELISA ƒ 52 . • It binds both vWF and platelet GP Ib causing agglutination of formalinized platelets.Laboratory Diagnosis  vWF activity • also know as ristocetin cofactor activity. which can be quantified and compared to a standard curve to obtain ristocetin cofactor activity.

Used for diagnose Type 2B variant.  FVIII activity • one stage coagulation assay using FVIII deficient plasma 53 . ƒvWF multimers .electrophoresis  Ristocetin induced plt aggregation(RIPA) • measure affinity vWF binds to GP Ib by limiting [ristocetin].

Hemophilia B And von Willebrand Syndrome 54 .Comparison Of Hemophilia A.

55 .

56 .

Acquired Coagulation Disorders Disseminated Intravascular Coagulation (DIC) by Sreeram Naidu .

• Is considered an “acquired bleeding disorder” • Is not a disease entity but an event that can accompany various disease processes • Is an alteration in the blood clotting mechanism:abnormal acceleration of the coagulation cascade. hemorrhage occurs simultaneously • Is a Paradoxical clinical presentation “clotting and hemorrhage” . resulting in thrombosis • As a result of the depletion of clotting factors.

a systemic activation of the coagulation system simultaneously leads to thrombus formation (compromising blood supply to various organs) and exhaustion of platelets and coagulation factors (results in hemorrhage).Pathophysiology • In DIC. This is a disruption of body homeostasis. .

necrosis 4) Leads to multi organ dysfunction .Thrombosis-brief period of hypercoagulability 1) Coagulation cascade is initiated. causing widespread fibrin formation 2) Microthrombi are deposited throughout he microcirculatory 3) Fibrin deposits result in tissue ischemia. hypoxia.

Fibrinolysis -period of hypocoagulability (the hemorrhagic phase) 1) Activates the complement system 2) Byproducts of fibrinolysis (fibrin/fibrin degradation products(FDP)) further enhance bleeding by interfering with platelet aggregation. fibrin polymerization. & thrombin activity 3) Leads to bleeding .


burns • Vascular abnormalities(aneurysm. e. snake bites.Underlying Conditions • Infection/sepsis • Trauma • Obstetrics(amniotic fluid embolism.g.g pancreatitis.placental abruption. solid tumour and leukemias • Tissue destructions. • Severe liver failure • Malignancy. ABO incompatibility. liver hemangioma) • Toxic/immunological. e. pre-eclampsia. recreational drugs .

dehydration. • Blood component therapy. such as fresh frozen plasma. cryoprecipitate and platelets.Management • Treatment is aimed at underlying cause • Often require intensive care to deal with concomittant issues. such as acidosis. renal failure and hypoxia. should be given if the patient is bleeding but should not be given routinely based on coagulation tests and platelet counts alone .

<100=1. >6s=2 5)Fibrinogen >1g/L=0. strong=3 4)Prolonged prothrombin time <3s=0. no increase=0. <50=2 3) Elevated fibrin degradation products. >3s but <6=1. <1g/L=1 TOTAL SCORE >5= compatible with overt DIC <5= Repeat monitoring over 2 days . moderate=2.ISTH (International Society For Thrombosis and Haemostasis) 1) Presence of an associated disorder 2) Platelets >100=0.

• Some patients with sepsis-associated DIC benefit from treatment with activated protein C concentrate.• Prophylactic doses of heparin should be given. unless there is a clear contraindication. .

Coagulopathies in Pregnancy .

due to increase in the levels of plasminogen inhibitors.Physiological changes in coagulation during pregnancy • Coagulation system : Increase in levels of coagulation factors. VIII. mainly fibrinogen and factor VII. Pregnancy is a HYPERCOAGULABLE STATE. • • THUS. IX and X – from the beginning of the second trimester. . Highest in 3rd trimester Anticoagulant system : Decrease in levels of anti-thrombin III and protein S. Platelet count : Gradual Decrease. • Fibrinolytic system : Inhibition of the system.

Obstetric Shock(Septic Shock) 6. Deep Vein Thrombosis & Other thromboembolic phenomena . Anti Phospholipid Syndrome 7. Disseminated Intravascular Coagulation(DIC) 5. Von Willebrand’s disease (vWD) 2. Hemophilia 3. HELLP Syndrome 4.Coagulopathies in Pregnancy 1.

Von Willebrand’s Disease

Von Willebrand’s disease (vWD)
• This is an autosomal dominant inherited coagulopathy. It is a disorder affecting the von Willebrand factor (vWF), which is a part of the factor VIII complex. • The vWF helps in coagulation in two ways: 1. It combines with factor VIII to produce a procoagulant factor VIIIc. 2. It helps platelets to bind to the damaged endothelium.

Von Willebrand’s disease (vWD)
• There are 3 types of this disease: • Type 1: This is a mild to moderate bleeding disorder and there is a partial deficiency of vWF. • Type 2a: There is a qualitative defect in vWF. • Type 2b: There is a qualitative defect in vWF with increased binding to platelets causing mild thrombocytopenia. • Type3: This is a severe bleeding disorder in which there is a complete absence of vWF and reduced levels of factor VIII.

• Patients with von Willebrand’s disease have a prolonged bleeding time and normal platelet count except in type 2b disease

Labour and Delivery • During pregnancy there is a three to four fold increase in vWF. • If operative delivery is necessary the level has to be >50 IU dl-1. • Post-partum haemorrhage can occur as the levels of vWF fall to pre-pregnancy level.vWD . Women suffering with type 2 and 3 disorders do not improve during pregnancy. • Vaginal delivery is considered safe if vWF is > 40 IU dl-1. • DDAVP (desmopressin) and vWF concentrates are used to increase the levels of vWF. Patients suffering with Type 1 disorder improve during pregnancy as the vWF levels increase up to the normal range. .

• Epidural catheter should be removed immediately after delivery.vWD . • Regional anaesthesia is safe in patients with Type 1 disease.Anaesthesia • An experienced anaesthetist should give epidural anaesthesia. as the level of coagulation factors increase to normal levels. as there is increased risk of epidural haematoma due the decline in the coagulation factor levels. . • Central neuroaxial block is not recommended for women with type 2 and 3 diseases.

Haemophilia .

e. . • The clotting factor level activity is expected to be around 50% of the normal.Haemophilia A and B • Haemophilia A and B are X-linked disorders due to deficiency of factor VIII and factor IX respectively. • Females are usually carriers of this disease as they have only one affected chromosome. But a wide range of values has been reported as a result of random inactivation of one of the two X chromosomes. lyonization. • These women with low factor levels have the same risk of bleeding. • Haemophilia prolongs activated prothrombin time (aPTT). as do affected males. i.

• The levels of clotting factor should be maintained ≥ 50% of normal values. • The maternal factor levels do not rise significantly until the second trimester. .Haemophilia A and B – Antenatal Management • The pregnancy should be managed in close collaboration with a haematologist. Invasive procedure such as first trimester abortions can be complicated by serious haemorrhage. • It is recommended that the factor levels be checked at booking and at 28 and 34 weeks of gestation.

.Haemophilia A and B . Haemophilia B • Factor IX concentrates • Fresh frozen plasma.Treatment Haemophilia A • Factor VIII concentrates • Cryoprecipitate • Intranasal or intravenous DDAVP.

• If the factor level is < 50 IUdl-1 than prophylactic factor supplementation is needed to maintain levels ≥ 50 IUdl-1 throughout labour and up to 7 days post delivery. as safe for normal vaginal delivery • Plasma level ≥ 50 IU dl-1 is sufficient for caesarean section. • The levels of coagulation factor fall significantly to pre-pregnancy level after delivery and can cause delayed postpartum haemorrhage. .Haemophilia A and B – Labour and Delivery • Plasma level ≥ 40 IU dl-1 is generally regarded.

• It may be difficult to measure factor levels if patient presents late during labour.Haemophilia A and B-Anaesthesia • A detailed history of bleeding problems and full coagulation profile with factor VIII and IX levels should be sought. regional anaesthesia should not be considered. If coagulation factor levels were ≥ 50 IUdl-1 in the third trimester. . • The use of regional block is controversial. Unless factor levels are ≥ 50 IUdl-1. and aPTT is normal. an experienced anaesthetist can do epidural procedure if platelet count. aPTT and prothrombin time are normal. • The epidural catheter should be removed soon after delivery as factor levels fall quickly in the post-partum period.

HELLP Syndrome .

elevated liver enzymes (liver function) LP. Many investigators consider the syndrome to be a variant of preeclampsia. elevated liver enzyme levels and a low platelet count. But it may be a separate entity.low platelets counts (platelets help the blood clot) It is a syndrome characterised by hemolysis.HELLP Syndrome H. is an obstetric complication that is frequently misdiagnosed at initial presentation.hemolysis ( breakdown of red blood cells) EL. .

burr cells & schistocytes and an increase in bilirubin and LDH levels in blood. Thrombocytopenia has been attributed to increased consumption and/or destruction of platelets. subcapsular hematoma formation or hepatic rupture. The elevated liver enzyme are secondary to obstruction of hepatic blood flow by fibrin deposits in the sinusoids. in severe cases. The hemolysis is a microangiopathic hemolytic anaemia . intrahepatic hemorrhage. . 2. 3. leading to periportal necrosis and.HELLP Syndrome-Pathogenesis 1.Resulting in abnormal blood picture with spherocytes.

2.HELLP Syndrome-Diagnosis Symptoms: 1. Pain in Right Hypochondrium 2. Oedema(Not a useful marker) 3. 4. Generalised pain Epigastric pain Nausea. 3. Hypertension & Proteinuria . Vomiting Headache Signs: 1.

Abnormal Peripheral Blood film Serum Bilirubin >1. Laboratory Diagnosis: 1. 5.HELLP Syndrome-Diagnosis Because early diagnosis of this syndrome is critical. 4.3 g/dl Serum LDH >600 U/L Serum AST >70 U/L Platelet Count <150000/cu. any pregnant woman who presents with malaise or a viral-type illness in the third trimester should be evaluated with a complete blood cell count and liver function test. 3. (Most Reliable Indicator) .

Antihypertensive drugs . continued until it reaches 150000/cu. Magnesium Sulphate .mm) 3. Delivery 2. Labetolol.prophylaxis against seizure 4.HELLP Syndrome-Treatment 1. Blood products .mm. Nifedipine (goal is maintain DBP within 90-100mm Hg) 5. Corticosteroids (Both antenatal & postnatal-IV dose of 10mg Dexamethasone 12 hourly if platelet count <100000/cu.Hydralazine.


Biochemical evidence of end-organ damage or failure .DIC It is a systemic bleeding and clotting disorder seen in association with well-defined clinical situations and laboratory evidence of: 1.Inhibitor consumption 4.Fibrinolytic activation 3.Procoagulant activation 2.

Pathogenesis of DIC
Three main triggers
1. Endothelial damage to small vessels 2. Thromboplastin release 3. Pro-coagulant phospholipid production secondary to intravascular coagulation

End result Generation of thrombin with ↑ fibrin deposition

Causes of DIC in Pregnancy
1. 2. 3. 4. 5. 6. 7. 8. 9. Abruptio placenta Amniotic fluid embolism Retention of a dead fetus Abortion Intra uterine infections Purpura fulminans Pre-eclampsia and eclampsia Acute fatty liver of pregnancy Thrombotic thrombocytopenic purpura

S/S of DIC In Pregnancy
•Multiple bleeding sites •Bruising of skin, mucous membranes •Internal bleeding •Lack of blood supply to tissues (ischaemia) •Sudden onset of high fever, severe general malaise, and extensive purpura of the extremities •Petechiae, purpuric papules, blood-filled blisters and bluish fingers and toes

Laboratory Diagnosis of DIC In Pregnancy Sample: Blood Tests: • Platelet Count: Reduced (not very specific for DIC as many conditions that are associated w/ DIC have low platelets .g. GestationalThrombocytopenia.e. HELLP. Leukaemia) • • • aPTT & Prothombin Time: Prolonged FDP(Fibrin degradation product) & D-dimer: Increased Fibrinogen: Decreased(<100 mg/dl) . Sepsis.

Management of DIC in Pregnancy •Correction of underlying aetiology •Restoration and maintenance of blood volume •5% dextrose in lactated Ringer’s solution •Whole blood (if available) or packed erythrocytes •Antibiotics as indicated •Delivery of fetus and placenta as indicated .

Management of DIC in Pregnancy •Evacuation of uterus as indicated for retained or necrotic tissue •Replacement of clotting factors as indicated •Fresh frozen plasma •Cryoprecipitate •Platelets .

• This is the commonest cause of DIC in the parturient. . • Upto 30% of patients may develop coagulopathy.Placenta Abruptio • Premature separation of the placenta from the uterine wall. Bleeding in these patients can largely be concealed and retroplacental. • Fluid resuscitation to correct hypovolemia and early delivery to stop bleeding is essential.

Amniotic Fluid Embolism • This is a commonly fatal obstetric complication caused by introduction of amniotic fluid into the maternal circulation. • Treatment . Haemorrhage is inevitable due to DIC. • Pathogenesis . replacement of intravascular fluid volume and treatment of DIC form the treatment plan. . profound hypotension and arterial hypoxemia and coma. with a decrease in cardiac output and blood pressure.There is no specific treatment.The entry of amniotic fluid into the pulmonary circulation results in (1) pulmonary vascular obstruction.Sudden onset of respiratory distress. Cardiopulmonary resuscitation. (2) pulmonary hypertension with cor pulmonale (3) ventilation perfusion mismatches causing severe arterial hypoxemia. • Symptoms .

Antiphospholipid Syndrome .

Primary . Anticardiolipin antibody 2.isolated 2. It is a multisystem disorder (skin. etc.) Can be: 1.Antiphospholipid Syndrome Defined as a persisting antiphospholipid antibody associated with thrombosis &/or pregnancy morbidity. usually SLE. Secondary . rheumatoid arthritis Caused by 2 types of autoantibody: 1. also myaesthenia gravis. thrombocytopenia. Lupus anticoagulants . valves.associated with another autoimmune disease.

IgG titers have been correlated with thrombosis. 2. IgM.Anticardiolipin antibodies are detected and quantified using an enzyme-linked immunosorbent assay and may be IgG. Testing for both Autoantibodies should be performed !! . 3.Antiphospholipid Syndrome-Diagnosis 1. or IgA. Lupus anticoagulants prolong phospholipids-dependent blood clotting times. Enzyme-linked immunosorbent assay .

pre-eclampsia. abruption • Iatrogenic damage(Anti-Ro: neonatal lupus & complete heart block) .APS-Pregnancy risks A) MATERNAL • Increased risk of thrombosis • Pre-eclampsia (10%) • Iatrogenic damage • SLE deterioration B) FETAL • Inhibition of trophoblast invasion-1st trimester loss • Placental dysfunction growth restriction & death.

Early intervention .APS : Treatment Principles 1. Close obstetric surveillance by a multidisciplinary team 3. Aspirin +/.LMW Heparin 2.

SLE & Pregnancy • Pregnant women who are also SLE patients are considered as under ‘high risk’ of developing Lupus Flare. renal or cardiac abnormality. whilst stillbirth & IUGR may occur. the baby may have a complete heart block due to antibody transfer. • If mother has “Anti-Ro-antibody’ . • There may be repeated abortions (due to antiphospholipid antibody). • Pregnancy should be avoided if there is neurological. .

. Diuretics in case of renal involvement. 2. • Mother should consult physician with regular Coagulation marker studies. Low dose Aspirin and/or LMW Heparin. urinary & Immunological studies.SLE & Pregnancy • Mother should consult obstetrician for safe maintenance & outcome of pregnancy. • Treatment: 1. but Dexamethasone and Betamethasone are contraindicated. Steroids: only Prednisone or prednisolone are safe. 3.

DVT & Other Thromboembolic Phenomena .

S •Previous history of thromboembolism •Prolonged hospital stay & immobility •Paraplegia .DVT & Other Thromboembolic Phenomena-Risk Factors •Pregnancy – is itself a hypercoagulable state . •Parity 3 or more •Obesity BMI > 30 •Smoking •Pre-eclampsia •Gross varicose veins •Inflammatory disorders (Active IBD) •Caeserean section. particularly emergency C. •Maternal age > 35 years.

DVT & Other Thromboembolic Phenomena-Risk Factors • Family history of thromboembolism.e. • Thrombophilia i. protein C or protein S.e. Congenital deficiency of antithrombin III. & presence of factor V leiden. polycythaemia vera • Intravenous drug use • Hyperemesis/dehydration • Surgery at anytime in pregnancy • Multiple pregnancy assisted reproductive therapies • Ovarian hyperstimulation syndrome • Long distance travel . • Anti – cardiolipin syndrome or presence of lupus inhibitor • Myeloproliferative disorders i.

Symptoms : Pain & swelling in the leg (left-sided DVT > right-sided 2. Tender calf muscles. accurate in 95% . A difference of > 2cm in the circumference at identical sites of legs IV. safe . Increase temperature of the leg. Positive Homan's sign. due to compression of the left iliac v by right iliac a and ovarian a) 1. Investigations : I. III. Ascending venography .Deep venous thrombosis (DVT): DVT & Other Thromboembolic Phenomena DVT because of relative increased venous stasis on the left. II. Signs : I. II. Doppler U/S – Noninvasive . 3.

and sudden collapse in massive PE 2.Signs : Cyanosis . Symptoms : Sudden onset of dyspnoea. chest pain.Investigations : • CXR • ECG • Respiratory alkalosis and low PCO₂ • Ventilation & perfusion lung scan • Pulmonary angiography. . cough & haemoptysis. 3.DVT & Other Thromboembolic Phenomena Pulmonary embolism (PE) : 1. rapid breathing & jugular veins distention.

DVT & Other Thromboembolic Phenomena-Treatment 1. followed by long term therapy. High Molecular Weight Heparin: given I/V •Efficacy is monitored by measuring APTT which should be 2X control value. . •Duration is for 2-3 months during pregnancy. Low Molecular Weight Heparin: S/C 2 mg/kg/d in 2 divided doses OR 2. Treatment of Acute Phase: By therapeutic dose of Heparin. either: 1.

Low Molecular Weight Heparin: S/C 40mg once daily OR B.5X control) LMWH and warfarin are safe to use in lactating mothers . High Molecular Weight Heparin: given I/V 5000 IU twice daily (monitored by plasma Heparin level) 2. By maintenance dose of Heparin.DVT & Other Thromboembolic Phenomena-Treatment 2. either: A. Long Term Therapy: By Any of the Following 1.5-5mg twice daily. (Monitored by INR=2 or & by PT 2=2. Warfarin orally 2.

Photophobia 7. Fever and leukocytosis . Impaired consciousness 4. • Clinical features: 1.Cerebral Vein Thrombosis Uncommon incidence 1 in 10. Signs of raised intracranial pressure 5. Focal signs such as hemiparesis 8.000 but associated with high mortality rate. Headache 2. Seizures 3. Vomitting 6.

subarachnoid hemorrhage and herpes encephalitis • CT scan – detect intracerebral bleeding • MRI . Diagnosis • DDx – eclampsia.Cerebral Vein Thrombosis Pathogenesis • Hypercoagulable postpartum state and possible trauma to endothelial lining of cerebral sinuses and veins during labour.

Cerebral Vein Thrombosis Management • Hydration • Anticonvulsants • Anticoagulation .


dental procedures. child birth Family history of bleeding disorders Known personal history of bleeding disorders (e. hemophilia. NSAID's) Hematologic malignancies Chemotherapy . aspirin.• History questions related to perioperative hemostasis Excessive bleeding or bruising with minor trauma.g. surgery. von Willebrand Disease) Liver disease Alcohol intake Medication use (especially anticoagulants.

is considered sufficient for most surgical procedures. or less.Laboratory Testing • Prothrombin Time (PT)/International Normalized Ratio (INR) and Platelet Count. obtaining a full coagulation panel is reasonable.5. • Mixing study • Platelet Function Screen . although a lower INR may be appropriate for high risk procedures • INR is elevated. Prothrombin Time: • INR of 1.

Interventions • Factor Deficiencies For patients with hepatic impairment or nutritional deficiency supplementation with vitamin K (phytonadione) is appropriate to consider pre and postoperatively. • Oral vitamin K therapy (5-10 mg po daily) • IV vitamin K (10mg/ single dose) • Supplement coagulation factors with fresh frozen plasma (FFP) if bleeding or need urgent procedures .

Platelet Dysfunction: • Infusion of donor platelets (typically a single 6-pack) is usually effective in restoring normal platelet function. .


References  Tom Lissauer. Pg 394. 120 . 7th Edition. 4th Edition. Pg 320328. Ghai Essential Paediatric. Graham Glayden. Hematological disorders.  OP Ghai.399. Mosby Elsevier. Illustrated Textbook of Paediatrics. CBS. Arvind Bagga. Vinod Paul.

Chapter 24 – Blood disease . Chapter 8 – Haematological disease • Nicky R . 21st Edition. Ralston.References • MF Murphy.Colledge. Brian R. JS Wainscoat and KJ Pasi. Stuart H. Walker. “Kumar and Clark’s Clinical Medicine”. “Davidson’s Principles and Practice of Medicine”. 8th Edition.