Hemorrhagic diathesis 2

patho

1. Dr. Ramesh Dhakhwa, MD Hemorrhagic diathesis II (Coagulation disorders)

2. Bleeding disorders 4 categories: Bleeding disorders due to vascular abnormalities Bleeding disorders due to platelet abnormalities Disorders of coagulation factors Combination of all of the above (Disseminated Intravascular Coagulation / DIC)

3. Coagulation disorders Factor VIII – hemophilia A Factor IX - Hemophilia B Christmas disease

4. Incidence X linked recessive 1 in 5000 males Approx. 80% have factor VIII deficieny 20% have factor IX deficiency In approx. 30%, no positive family history of the disease - ? Genetic mutation.

5. Factor VIII deficiency Factor VIII ( antihemophilic factor) : protein that circulates in the plasma and functions in the intrinsic pathway of fibrin formation . Factor IX deficiency Factor IX – vitamin K dependent serine protease that functions in the intrinsic pathway of fibrin formation .

6. Clinical symptoms Hemarthrosis , esp. in the knee – most common feature of severe hemophilia. Subcutaneous hematomas – begin with slight trauma and spread to involve a large mass of tissue. Intramuscular hemorrhages – may result in contracture and deformity

7. Prolonged bleeding Primary hemostasis adequate to stop bleeding from a minor cut, but because of deficient fibrin stabilization, the platelet plug is dislodged – bleeding begins a second time. Hematomas around tongue and throat Hemorrhages from the nose, mouth, gums and other mucous membranes Others : hematuria and excess bleeding from dental extractions

8. Laboratory aspects Laboratory screening tests – Prolonged APTT Platelet count – normal Bleeding time – normal PT – normal Definitive diagnosis – Specific factor assay

9. Therapy Factor VIII deficiency Cryoprecipitate : prepared by freezing a unit of plasma and collecting the precipitate that forms on thawing. Contains factor VIII, factor XIII, fibrinogen and von Willebrand factor Factor VIII concentrate Deamino -D- arginine vasopressin ( DDAVP )

10. Factor IX deficiency : Treated with plasma or with concentrates that also contain factors II, VII, and X (prothrombin complex concentrates)

11. Disseminated Intravascular Coagulation (DIC) DIC is an acute, subacute , or chronic thrombohemorrhagic disorder characterized by the excessive activation of coagulation, which leads to the formation of thrombi in the microvasculature of the body. It occurs as a secondary complication of many different disorders.

12. Sometimes the coagulopathy is localized to a specific organ or tissue. As a consequence of the thrombotic diathesis there is consumption of platelets, fibrin, and coagulation factors and, secondarily, activation of fibrinolysis.

13. Conditions Associated With DIC Infectious/Septicemia Bacterial Gm - / Gm + Viral CMV Varicella Hepatitis Fungal Intravascular hemolysis Acute Liver Disease Tissue Injury trauma extensive surgery tissue necrosis head trauma Obstetric Amniotic fluid emboli Placental abruption Eclampsia Missed abortion

14. Conditions Associated With DIC Malignancy Leukemia Metastatic disease Cardiovascular Post cardiac arrest Acute MI Prosthetic devices Hypothermia/Hyperthermia Pulmonary ARDS/RDS Pulmonary embolism Severe acidosis Severe anoxia Collagen vascular disease Anaphylaxis

15. Pathogenesis Activation of coagulation: by release of tissue factor Thrombotic phase: platelet adhesion and aggregation with formation of thrombi and emboli throughout the microvasculature Consumption phase: consumption of coagulation factors and platelets Secondary fibrinolysis: causes breakdown of fibrin resulting in fibrin degradation products in circulation

16. Pathophysiology of disseminated intravascular coagulation

17. Clinical Manifestations of DIC

18. Clinical Manifestations of DIC

19. Microscopic findings in DIC Fragmented RBCs Paucity of platelets

20. Laboratory diagnosis Thrombocytopenia platelet count <100,000 or rapidly declining Prolonged clotting times (PT, APTT) Presence of Fibrin degradation products or positive D-dimer

21. Treatment Prompt treatment of primary disease. Heparin therapy. Platelet transfusions. Replacement therapy with coagulation factors.

22. Thank you