Haemostasis Year 4 Paediatrics Notes OmpathStudy

Haemostasis Year 4 · Paediatrics Collection: 4TH YEAR ALL NOTES / PAEDS / PAEDS 4.3 / Munge / HAEMATOLOGY -- Slide 1 Bleeding Disorders Dr Rose Munge Slide 2 Pathology Congenital deficiency of an individual procoagulant protein leads to a bleeding disorder, whereas deficiency of an anticoagulant (clotting factor inhibitor) predisposes the patient to thrombosis.\nA primary illness (sepsis) and its secondary effects (shock and acidosis) activate coagulation and fibrinolysis and impair the host's ability to restore normal hemostatic function.\nWhen sepsis triggers disseminated intravascular coagulation, platelets, procoagulant clotting factors, and anticoagulant proteins are consumed, leaving the hemostatic system unbalanced and prone to bleeding or clotting.\nNewborn infants and patients with severe liver disease have synthetic deficiencies of both procoagulant and anticoagulant proteins predisposing the patient to be predisposing to both hemorrhage and thrombosis with mild or moderate triggers that result in major alterations in the hemostatic process. Slide 3 The dual mechanisms of activating clotting have been termed the intrinsic (surface activation) and extrinsic (tissue factor–mediated) pathways.\nPT measures the activation of clotting by tissue factor (thromboplastin) in the presence of calcium.\nAddition of tissue factor causes a burst of factor VIIa generation.\nThe tissue factor–factor VIIa complex activates factor X.\nWhether factor X is activated by the intrinsic or the extrinsic pathway, factor Xa on the platelet phospholipid surface complexes with factor V and calcium (the “prothrombinase” complex) to activate prothrombin to thrombin (also referred to as factor IIa ).\nOnce thrombin is generated, fibrinogen is converted to a fibrin clot, the end-point of the reaction Slide 4 PT is not prolonged with deficiencies of factors VIII, IX, XI, and XII. In most laboratories the normal PT value is 10-13 sec.\n PT has been standardized using the international normalized ratio (INR ) so that values can be compared from one laboratory or instrument to another.\n This ratio is used to determine similar degrees of anticoagulation with vitamin K antagonists, such as warfarin. Slide 5 The intrinsic pathway involves the initial activation of factor XII, which is accelerated by 2 other plasma proteins, prekallikrein and high-molecular-weight kininogen.\nIn the clinical laboratory, factor XII is activated using a surface (silica or glass) or a contact activator, such as ellagic acid.\nFactor XIIa in turn activates factor XI to factor XIa, which then catalyzes factor IX to factor IXa.\nOn the platelet phospholipid surface, factor IXa complexes with factor VIII and calcium to activate factor X (“tenase” complex). This process is accelerated by interaction with phospholipid and calcium at the steps involving factors V and VIII. An isolated deficiency of a single clotting factor may result in isolated prolongation of PT, PTT, or both, depending on the location of the factor in the clotting cascade.\nThis approach is useful in determining hereditary clotting factor deficiencies; however, in acquired hemostatic disorders encountered in clinical practice, more than 1 clotting factor is frequently deficient, so the relative prolongation of PT and PTT must be assessed Slide 6 Measurement of PTT as performed in the clinical laboratory is actually “activated” PTT; most refer to it as PTT.\nThis test measures the initiation of clotting at the level of factor XII through sequential steps to the final clot endpoint. It does not measure factor VII, factor XIII, or anticoagulants.\nPTT uses a contact activator (silica, kaolin, or ellagic acid) in the presence of calcium and phospholipid.\nBecause of differences in reagents and laboratory instruments, the normal range for PTT varies among hospital laboratories. Slide 7 Hereditary Clotting Factor Deficiencies (Bleeding Disorders) Hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency) are the most common and serious congenital coagulation factor deficiencies.\nThe clinical findings in hemophilia A and hemophilia B are virtually identical. Hemophilia C is the bleeding disorder associated with reduced levels of factor XI.\nReduced levels of the contact factors (factor XII, highmolecular- weight kininogen, and prekallikrein) are associated with significant prolongation of activated partial thromboplastin time (aPTT; also referred to as PTT ), but are not associated with hemorrhage Slide 8 Factor VIII or Factor IX Deficiency (Hemophilia A or B) Deficiencies of factors VIII and IX are the most common severe inherited bleeding disorders. Pathophysiology Factors VIII and IX participate in a complex required for the activation of factor X. Together with phospholipid and calcium, they form the “tenase,” or factor X– activating, complex.\nIn vivo, the complex of factor VIIa and tissue factor activates factor IX to initiate clotting.\nIn the laboratory, prothrombin time