Hemostasis defects Flashcards
Protime/International Normalized Ratio (PT/INR) - what is it testing and ddx
measures extrinsic coag pathway
-Ca2+ & thromboplastic + citrated plasma -> measure clot time
- Prolonged with Factor II, VII, V, X, fibrinogen deficiencies, vitamin K deficiency, liver disease or patient on warfarin.
- If protime is more prolonged than PTT: liver disease, vit K deficiency, warfarin or rat poison
Activated Partial Thromboplastin Time (aPTT) - what is it testing and ddx
- measures intrinsic coag pathway
- surface activating agent and phospholipid + citrated plasma -> activated plasma recalcified -> measure clot time
- Prolonged PTT indicates: Hemophilia (deficiency in factor VIII, IX, or XI), acquired hemophilia, severe von Willebrand disease, heparin in sample (an anticoagulant), fibrin split products. Also can indicated Factor XII deficiency or lupus anticoagulant (both non-bleeding disorders).
- If PTT is relatively more prolonged than PT: Disseminated intravascular coagulation (DIC)
Thrombin Time (TT)
plasma + excess thrombin -> detects fibrinogen, fibrin split products or heparin levels
Bleeding time
measures platelet function, vessel wall and skin integrity
-a template device makes a cut on the forearm and time to clot is measured (2-9 minutes is normal).
- Prolonged time indicates: vascular disorders (thrombocytopenia, DIC, etc) and von Willebrand Disease–not by other coagulation factors such as haemophilia.
- Aspirin and other cyclooxygenase inhibitors can prolong bleeding time significantly.
Platelet Function Analyzer (PFA):
determines an in vitro bleeding time with agonists
Other tests
- Fibrinogen
- FSP
- Coag factor testing
- Mixing test
clinical features and molecular basis for hemophilia A and B
-linked deficiency in Factor VIII (A) or IX (B), males primarily affected and carrier females often symptomatic, elevated PTT is only abnormal screening test. Many are new mutations. Diagnosis: screen males with unexplained hematomas, bruises, bleeding.
Complications: soft tissue hemotoma, joint bleeding, CNS bleeds (cause of death), retroperitoneal or psoas bleeds. Assay factor activity to distinguish A from B.
Treatment: molecular diagnostics used, recombinant synthetic factor treatment is effective, genetic cure likely.
clinical features and molecular basis for factor VII deficiency
PTT prolonged, post-operative bleeding, autosomal recessive, variable incidence in population.
Describe the role of liver disease in coagulopathy
Decreased synthesis of most factors, decreased vitamin K dependent carboxylation of II, VII, IX and X, decreased fibrinogen production, consumption of platelets
-Prolonged PT/INR (low II, VII, V, X), Prolonged PTT (low IX and X), Prolonged TT (low fibrinogen and increased fibrinolysis).
dx and tx of liver disease in coagulopathy
replace factors with plasma infusion, augment vit K reactions, recombinant factor VII (VII has the shortest half life), platelet transfusions
DIC occurs when
the coagulation cascade is activated in the vascular system causing fibrin and platelet microthrombi to form plugs in capillaries which result in tissue infarction while at the same time, some factors and platelets are being consumed. Ultimately, this results in multiple coagulation factor deficiencies and hemorrhage is often the result
DIC can be caused by
massive trauma, hemorrhagic or septic shock, amniotic fluid embolism, burns, acute leukemia, and drug reactions.
The most common laboratory findings for DIC are
that the fibrinogen level has decreased and the platelet count is low.
The key thing to note to distinguish DIC from liver disease is that
in DIC the PTT is increased relative to the protime and that the protime is usually the least affected. When the underlying disorder is corrected, the fibrinogen will return to normal and the platelet count will rise.
what a lupus anticoagulant is
very common acquired abnormality which results in a hypercoaguable state. The “lupus anticoagulant” is an IgG antibody that binds phospholipid in the platelet or endothelial membrane. The presence of lupus anticoagulant results in syndrome called Antiphospholipid Antibody Syndrome (APS).
