Coagulation Disorders

Coagulation Disorders

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  COAGULATION DISORDERS Abhineet Dey, 4th Semester GAUHATIMEDICAL COLLEGE AND HOSPITAL Guwahati
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  COAGULATION DISORDERS Definition: These area group of disease caused due to deficiency of clotting factors and lead to defects in normal clot formation process.
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  CLASSIFICATION Based on originthese disorder are of two types, 1. Hereditary Coagulation Disorder These inherited plasma coagulation disorders are due to qualitative or quantitative defect in single coagulation factor. a. Sex Linked (X) Disorders e.g. Classical haemophilia or haemophilia A, Christmas disease or haemophilia B b. Autosomal Disorders e.g. von Willebrand’s disease 2. Acquired Coagulation Disorder These are characterized by deficiency of multiple coagulation factor. a. Vitamin K deficiency b. Coagulation disorder of liver disease c. Fibrinolytic defects d. Disseminated intravascular resistance.
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  HEREDITARY COAGULATION DISORDERS
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  CLASSICAL HAEMOPHILIA oIts isthe second most common cause of hereditary coagulation disorder. oIt is inherited as sex (X) linked recessive trait, so more common in males while females are the carriers.
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  CLASSICAL HAEMOPHILIA (CONTD.) Pathogenesis: A.Quantitative reduction in factor VIII (in 90% of cases). B. Normal or increased level of factor VIII with reduced activity (in 10% of cases). Factor VIII is synthesized in hepatocytes. In the intrinsic coagulation pathway factor IXa complexes with factor VIIIa, this complex in the presence of platelets, PL and Ca2+ activates factor X to Xa.
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  CLASSICAL HAEMOPHILIA (CONTD.) IXIXa VIIIa PL Ca2+ X Xa Disruption of the Intrinsic Coagulation Pathway (Due to the absence of activated Factor VIII)
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  CLASSICAL HAEMOPHILIA (CONTD.) ClinicalFeatures: Symptoms are elicited when factor VIII activity is reduced to less than 25%. Patient suffers bleeding for hrs to days and severity is based on plasma level of factor VIII activity. Recurrent painful haemarthroses and muscle haematoma and sometimes haematuria. Lab Diagnosis: a. Whole blood coagulation time is raised in severe cases only. b. Prothrombin time is usually normal. c. Activated partial thromboplastin time (APTT or PTTK) is typically prolonged. d. Specific assays for factor VIII shows lowered activity (50% activity of factor VIII in female carriers). Treatment:
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  CHRISTMAS DISEASE/HAEMOPHILIA B oX linkedrecessive disease. oRarer than haemophilia A. oIncidence Ratio is 1: 100000 male birth. oInheritance pattern and clinical features are similar to classical haemophilia. Lab Diagnosis: Assay of factor IX level which is lowered. Other lab findings are similar to haemophilia A. Treatment: Infusion of fresh frozen plasma or plasma enriched with factor IX.
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  VON WILLEBRAND’S DISEASE oMostcommon hereditary coagulation disorder. oInherited as autosomal dominant trait. oIncidence rate is 1:1000 of either sex. oOccurs due to qualitative or quantitative defect in vWF. Factor VIII-von Willebrand complex Consists of 99% vWF and 1% factor VIII. They circulate together as a unit and perform important function in clotting and facilitate platelet adhesion to sub endothelial collagen. Clinical Features: Spontaneous bleeding from mucous membranes, excessive bleeding from nose and menorrhagia.
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  VON WILLEBRAND’S DISEASE (CONTD.) Types: Type-1disease It is the most common and is characterized by mild to moderate decrease in plasma vWF (50% activity). Synthesis of vWF is normal but the release of its multimers is inhibited. Type-2 disease It is much less common and is characterised by normal or near levels of vWF which is functionally defective. Type 3 disease It is extremely rare and is most severe form of disease. These patients have no detectable vW activity and may have sufficiently low level of factor VIII.
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  VON WILLEBRAND’S DISEASE (CONTD.) LabDiagnosis:  Prolonged bleeding time.  Normal platelet count.  Reduced plasma vWF concentration.  Defective platelet aggregation with ristocetin, an antibiotic.  Reduced factor VIII activity. Treatment: Cryo-precipitates or Factor VIII concentrates
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  ACQUIRED COAGULATION DISORDERS
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  VITAMIN K DEFICIENCY VitaminK serves as a cofactor in the formation of 6 prothrombin complex proteins (Vitamin K dependent coagulation factors) synthesized in the liver: Factor II, VII, IX, X, Protein C and Protein S. Causes of Vitamin K deficiency:  Obstructive jaundice.  Chronic diarrhoea.  Liver disease.  Haemorrhagic states in infants.
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  VITAMIN K DEFICIENCY(CONTD.) Lab Diagnosis: Prolonged PTT and PTTK. Treatment: Parenteral administration of Vitamin K causes complete recovery in 48 hrs.
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  COAGULATION DISORDER INLIVER DISEASE Factors promoting coagulation Factors inhibiting coagulation Synthesis of Coagulation Factors. Synthesis of Anti-thrombin 3, Protein C and Protein S Clearance of Fibrinolytic enzymes Clearance of Activated Factors • Liver is the site of synthesis and metabolism of Coagulation Factors. • Liver disease leads to hypercoagulability and predispose to develop DIC and systemic fibrinolysis.
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  COAGULATION DISORDER INLIVER DISEASE (CONTD.) Major causes of bleeding in liver disease are:  Morphologic lesions: Portal hypertension , peptic ulceration, gastritis.  Hepatic dysfunction: Impaired hepatic synthesis of coagulation factors and coagulation inhibitors, impaired absorption and metabolism of Vitamin K, failure to clear activated coagulation factors.  Complication of therapy Massive transfusion leading to platelet and clotting factors dilution, following heparin therapy. Lab Diagnosis: Prolonged PTT and PTTK, mild thrombocytopenia, normal fibrinogen level and decreased hepatic stores of Vitamin k.
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  DISSEMINATED INTRAVASCULAR COAGULATION Also calledas defibrinate syndrome or consumption coagulopathy is a complex thrombo-haemorrhagic disease occurring as secondary complication of some systemic disease. Major disorders associated with DIC:  Obstetrics Complications- Abruption placentae, retained dead foetus, septic abortion, amniotic fluid embolism, toxaemia.  Infections- Gram negative sepsis, meningococcemia, rocky mountain spotted fever, malaria.  Neoplasms- Carcinoma of pancreas, prostate, lung and stomach.  Massive Tissue Injury- Traumatic, burns, extensive surgery.  Miscellaneous- Acute intravascular haemolysis, snake bite, giant haemangioma, shock, heat stroke. Pathogenesis:
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  DISSEMINATED INTRAVASCULAR COAGULATION (CONTD.) Pathophysiologyof Disseminated Intravascular Coagulation
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  DISSEMINATED INTRAVASCULAR COAGULATION (CONTD.) ClinicalFeatures: a. Widespread fibrin deposition within microcirculation leading to ischemia of organs like kidney and brain. b. Bleeding diathesis- ensues as the platelets and clotting factors are consumed and there are secondary release of plasminogen activator but also digest Factor V and VIII there by reducing their concentration further. Lab Diagnosis: a. Reduced platelet count. b. Blood film shows microangiopathic haemorrhagic haemolytic anaemia. c. PT, TT,APTT are prolonged. d. Plasma fibrinogen level is reduced.
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  DISSEMINATED INTRAVASCULAR COAGULATION (CONTD.) Treatment: Anticoagulantslike heparin or coagulants contained in fresh frozen plasma, underlying disorder must be treated simultaneously.
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