Bleeding Disorders & Thrombocytopenia PDF

Lesson-6-"Bleeding Disorders 3 Thrombocytopenia" Hemostasis: normally in response to injury or incision: (ultimate goal is try and stop bleeding by forming a platelet-fibrin clot at the site of injury) primary hemostasis (platelets...

Lesson-6-"Bleeding Disorders 3 Thrombocytopenia" Hemostasis: normally in response to injury or incision: (ultimate goal is try and stop bleeding by forming a platelet-fibrin clot at the site of injury) primary hemostasis (platelets) Secondary hemostasis (coagulation factors) stages of hemostasis: ○ Primary hemostasis: ◆ Vasoconstriction (immediate effect) ◆ Platelet adhesion (occurs within seconds) ◆ Platelet aggregation (occurs with in minutes) ○ Secondary hemostasis: ◆ Coagulation factor activation ◆ Fibrin formation (minutes) ○ Fibrinolysis: (clot dissolving system) ◆ Fibrinolysis warning (minutes) Primary Hemostasis ◆ Dissolution of the clot (hours) Primary hemostasis (vasoconstriction): first response to trauma When vascular epithelium is damaged -the following is synthesized-: ○ Thromboxane A2 (causes the vasoconstriction) ○ Nitric oxide ○ Tissue factor (initiates secondary coagulation) ○ Collagen (blocks blood flow) Primary hemostasis (platelet adhesion) platelets should be sufficient in number and function normally and the following substances should be intact for primary hemostasis to occur: ○ VWF ○ Collagen ○ Glycoprotein IIb-IIIa ○ glycoprotein Ib-IX Primary hemostasis disorders: bleeding starts with simple trauma (immediately) Bleeding is superficial simple stuff like petechaie, purpura, & ecchymosis begin to form. Can be controlled with simple precautions most important test to be done is bleeding time, therefore patients with high bleeding time usually have a primary hemostasis disorder. Secondary hemostasis; general info: (primary hemostasis is weak) ○ bleeding starts in 30-45 minutes after trauma ○ if secondary hemostasis does not occur after the primary one, the platelet plug that was formed (in primary hemostasis) disappears within 30-45 minutes, and eventually bleeding occurs. ○ for secondary hemostasis to occur; all coagulation factors must be present (I toXIII) ◆ Factors II, VII, IX, & X are vitamine K-dependent coagulation factors ○  ○ patients with secondary hemostasis disorders are usually seen with : ◆ Hematoma ◆ Hemarthrosis ◆ GI and CNS system bleeding ○ PTZ/INR and APTT are used in the diagnosis of secondary hemostasis disorders. Important clinical manifestations to be aware of : bleeding patterns: ○ vascular and platelet-related hemorrhages usually cause mucous membrane and skin bleeding ○ Coagulation disorder bleeding/hemorrhages usually cause deep skin and intra articular bleeding Platelets: normal value (150,000-450,0000 per/microliter of blood) some are produced by megakaryocytes (in bone marrow), and the most important growth factor stimulating megakaryocytes is thrombopoietin. IL-6 and GM-CSF also have a stimulating effects on megakaryocytes 1/3rd of platelets is stored in spleen (spleen is the main side of destruction) Fibrinolysis: degradation of fibrin webs formed in the body The substance that enables fibrinolysis is plasmin Fibrinolysis is vital in preventing the spread of fibrin Most important fibrin degeneration product is d-dimer (used for laboratory purposes) What can bleeding be due to? vascular disease———> DIC Platelet deficiency or dysfunction———> thrombocytopenia Coagulation disorders (factor deficiencies & inhibitor development)———> hemophilia Thrombocytopenia: platelet count falling below the lower limit (The patient's platelets were 20,000 without any other cause—>That's when we think of HIT.. Coagulation disorders: hereditary: ○ Hemophilia A & B ○ Von Willebrand disease ○ Rare factor deficiencies Acquired ○ Liver disease ○ Vitamine K deficiency ○ Warfarin overdose ○ DIC Disseminated intravascular coagulation (DIC) = consumption coagulopathy, defibrillation syndrome) general info: ○ presence of an underlying primary disease ○ excessive and uncontrolled activation of the coagulation system Most common causes: ○ sepsis ○ Trauma and tissue damage ○ Cancer ○ Pregnancy complications characteristics : ○ systemic process with thrombosis and bleeding ○ increased procoagulants ○ Excessive fibrin formation in the circulation ○ Decreased clotting factors ○ Organ damage, therefore best tx is to treat underlying damage/cause Clinical finding: ○ bleeding: (consumption-plasmin formation): ◆ spontaneous bruises ◆ peteshi ◆ GI bleeding ◆ Pol hemorrhage ◆ Bleeding from venous access sites and surgical incision sites ◆ Intracranial hemorrhage ○ Thrombosis: (thrombin formation) ◆ kidney failure ◆ coma ◆ Liver failure ◆ Respiratory failure ◆ Skin necrosis(purpura fulminans) ◆ Gangrene ◆ Venous thromboembolism diagnosis: ○ tests showing factor and platelet consumptions ◆ PT ◆ fibrin monomer Fibr  ◆ thrombin time ◆ Fibrinogen level ◆ Platelet count ○ Test showing thrombin generation ◆ D-dimer ◆ Fibrin monomer ◆ Fibrinopeptides a and b ◆ Prothrombin fragment 1.2 ◆ Thrombin-antithrombin complex Treatment: ○ Treatment of the underlying disease must be started quickly. ○ Basic supportive treatment is administered most rapidly and intensively. ○ IV antibiotics in patients with sepsis, ◆ Such as uterine evacuation in the presence of abruptio placenta ○ Termination of pregnancy, hysterectomy if necessary ○ Good adjustment of cardiovascular hemodynamic balance ○ Protection of electrolyte balance ○ Ensuring gas exchange ○ Example: What should we do if the patient is diagnosed with AML M3 and DIC? ◆ We should give -ATRA* (All Trans Retinoic Acid). Thus, the procoagulant produced in the cytoplasm of promyelocytes decreases and the cause of DIC is eliminated.. Hemophilia: general info: ○ inherited bleeding disorder caused by a deficiency of factor VIII or IX ○ Intra-articular and intramuscular bleeding Important to differentiate: ○ factor VIII deficiency—-> hemophilia A ○ Factor IX deficiency—-> hemophilia B Clinical manifestations: ○ Easy ecchymosis formation in early childhood, the presence of spontaneous bleeding, especially intra-articular and intramuscular bleeding, and a history of longer than expected bleeding after trauma should suggest hemophilia. ○ The severity of bleeding findings is directly related to the degree of deficiency of factor VIII or IX. ○ Factor activity while patients with 5% show a “mild hemophilia” clinic.