Hemostasis and Thrombosis Flashcards

Flashcards covering disorders of hemostasis, thrombophilia, and related topics.

What is implied by coagulopathy?

Hemostatic defect if bleeding is from multiple sites, spontaneous and recurring, or uncontrolled/excessive.

What are the manifestations of a systemic bleed?

Petechiae, purpura, and ecchymosis

What does an anatomic bleed often indicate?

A clotting factor deficiency or defect (secondary hemostasis issue).

What are replacement products used from the blood bank?

Fresh frozen plasma, solvent/detergent treated plasma, cryoprecipitate, clotting factor concentrates, packed RBCs, and platelets.

What is Thrombophilia?

A condition that increases the risk of developing blood clots, e.g., Factor V Leiden or Antiphospholipid syndrome.

Define venous thrombosis.

Thrombi in veins related to decreased blood flow (stasis) and activation of the coagulation cascade, more common in lower limbs; can be superficial or deep.

What is the first step in arterial thrombus formation?

Damaged endothelium (atherosclerotic plaques) leading to platelet activation and coagulation cascade.

Name examples of thrombotic disorders.

Venous Thromboembolism (VTE), Deep Venous Thrombosis (DVT), Pulmonary Embolus (PE), Myocardial Infarct (MI), Stroke - Cerebrovascular Accident (CVA).

What are the two components in the coagulation system?

Clotting/Procoagulant and Fibrinolysis/Anticoagulant

What are the results of abnormal clotting?

Increased procoagulants, decreased fibrinolysis, or defects/deficiencies in coagulation factors or regulators.

What are some acquired thrombosis risk factors?

Trauma, surgery, immobilization, oral contraceptives, hormone replacement therapy, inflammation, infection, cancer, pregnancy, hypertension, poor diet, high cholesterol, smoking, obesity, previous thrombosis.

What characterizes hereditary Thrombophilia?

Deficiency/defect in regulator of hemostatic system, often autosomal dominant, clots occur at relatively young age, and positive history in kindred.

What is the effect of Factor V Leiden?

Causes activated protein C resistance, leading to prolonged clotting.

What is the role of Protein C and S?

Provide regulation of clotting via inhibition of Factors V & VIII.

What is the effect of Prothrombin G20210A?

Elevated Factor II levels, leading to more thrombin generation.

What is the role of Antithrombin (AT)?

Naturally occurring anticoagulant (SERPIN family) that inactivates all serine proteases and is enhanced by heparin.

What is the effect of Anti-Phospholipid Antibodies (APL)?

Increase risk of thrombosis and inhibit phospholipid dependent tests, often prolonging APTT.

What does testing for Hypercoagulability require?

Testing during remission, not on therapy, not close to thrombotic event, and screening based on clinical findings.

What is the role of TPA, urokinase, and streptokinase?

Thrombolytic therapy ("Clot-busting" drugs).

What are examples of drugs used mainly in arterial thrombosis?

Aspirin / Antiplatelet drugs (e.g., clopidogrel, ticlopidine).

Name other disorders involving thrombosis?

Thrombotic thrombocytopenic purpura (TTP), Disseminated intravascular coagulation (DIC), and Liver disease

What are the general causes for Thrombocytopenia?

Decreased production, increased destruction/consumption, abnormal distribution, and dilution.

What inherited conditions lead to decreased production of platelets?

Fanconi Anemia, TAR Syndrome (Thrombocytopenia Absent Radii), Wiskott-Aldrich Syndrome, and May-Hegglin Anomaly.

What are two causes of increased destruction/consumption of platelets?

Mechanical destruction/consumption (DIC, TTP, HUS) and Immunologic destruction (ITP).

What is the pathophysiology of Heparin-Induced Thrombocytopenia (HIT)?

Antibodies form to heparin/PF4 complex, leading to platelet aggregation and thrombosis.

What confirms diagnosis of HIT?

Serotonin release assay, Platelet aggregation method, ELISA, and Flow cytometry.

What is the mechanism of Thrombotic Thrombocytopenic Purpura (TTP)?

Caused by development of ULvWF (Ultra large von Willebrand factor multimers). Most patients have an autoantibody to vWF cleaving protein which inhibits its normal activity.

What are the signs/symptoms of TTP?

thrombocytopenia, hemolytic anemia with RBC fragments, renal abnormalities, fever, neurologic (CNS) problems

What is the mechanism of Hemolytic Uremic Syndrome (HUS)?

Often follows bacterial infection with E. coli O157:H7 or Shigella which release damaging toxins, leading to endothelial damage and thrombi.

What is occurring in Neonatal Alloimmune Thrombocytopenia (NAIT)?

Birth parent HPA-1a negative, Baby HPA-1a positive. Birth parent makes antibodies to foreign antigen. Antibodies cross placenta, attack baby’s platelets.

What condition may cause Thrombocytosis?

Platelet dysfunction AND Thrombosis

Name two causes for Thrombocytosis.

Reactive Thrombocytosis and Myeloproliferative Disorders

What are the general characterizations of Qualitative Platelet Disorders?

Clinical evidence of bleeding (usually superficial), but normal platelet count and normal plasma clotting factors (PT, APTT).

Name three Platelet Function Disorders

von Willebrand’s Disease, Bernard-Soulier Syndrome, and Hypergammaglobulinemia

What is Bernard-Soulier Syndrome?

Rare, autosomal recessive disorder with decreased GPIb-IX and absence of GPV on platelet surface, leading to adhesion defect - can’t bind vW factor.

What are typical signs/symptoms of Secondary Hemostasis disorders?

Deep tissue bleeding, life threatening bleeds, spontaneous Ecchymoses (bruise), but No petechiae (spots)

Is acquired or inherited more common for secondary hemostasis disorders?

Acquired much more common than inherited.

In inherited disorders, can both PT and APTT be prolonged?

No, inherited disorders affect single factors.

Is von Willebrand Disease a disorder of primary or secondary hemostasis?

Since platelets can't adhere, it is a disorder of primary hemostasis.

von Willebrand Disease is often difficult to diagnose becuase it is so mild, but what lab tests should you run?

Bleeding time, Platelet count, PT, APTT, PFA 100, and Platelet aggregation

What are the commonalities between laboratory and physiology when comparing Hemophilia A and vonWillibrand Disease?

APT prolonged in both, but VIII only decreased in Hemo A where vWf and VIII are decreased in vWD. BT and PFA100 are normal in Hemo A, vonWillibrand is prolonged.

Is Factor IX or Factor VIII deficiency more common?

Factor VIII (Hemophilia A) is more common (85% of cases).

What's the difference between Afibrinogenemia, Hypofibrinogenemia, and Dysfibrinogenemia?

Trace amounts, <100 mg/dL, and functional defect respectively.

Is bleeding in liver disease due to a single issue?

No, bleeding results from a combination of factors, including decreased factor synthesis, production of abnormal forms (PIVKAs), activation of fibrinolytic system, and thrombocytopenia.

In addition to PT and APTT, what lab tests should you expect to be abnormal in liver disease?

Bleeding Time, PFA 100, Platelet count, Thrombin clotting time, Fibrinogen, Platelet aggregation function, and FDP's.

There are several other acquired disorders besides factor deficiencies, name a few.

Vitamin K deficiency, Renal failure, Acquired hemophilia, and Acquired von Willebrand's

How would you identify an acquired circulating anticoagulant?

Increased PT, APTT in "normal" person with failure of normal plasma to correct.

What is the medical definition of DIC?

Severe, life-threatening, acquired syndrome triggered by tissue destruction.

What are the results of a DIC screen?

PT, APTT, Fibrinogen, and D-dimer.

If my coagulation tests (PT/aPTT) results are >1.5 times above midpoint of ref interval and patient is NOT on anticoag therapy -- what would you suspect?

bleeding disorder

What are common medical conditions that cause bleeding?

Conditions include hemophilia, von Willebrand disease, liver disease, and platelet disorders.

Differentiate between congenital and acquired bleeding disorders.

Congenital bleeding disorders are genetic and present at birth, while acquired bleeding disorders develop later due to factors like disease or medication.

What laboratory tests are used to screen for coagulopathies?

Tests include PT (Prothrombin Time), aPTT (Activated Partial Thromboplastin Time), and platelet counts.

What is the significance of Prothrombin Time (PT)?

PT measures the time it takes for blood to clot, helping to assess the extrinsic and common coagulation pathways.

Describe the risk factors associated with thrombosis.

Risk factors include immobility, obesity, hormonal therapy, age, and personal or family history of thrombosis.

What are hereditary thrombotic diseases (HTD)?

HTDs are genetic disorders that increase the risk of thrombosis, often due to deficiencies in anticoagulant proteins.

What deficiency is associated with antithrombin?

Antithrombin deficiency increases the risk of venous thromboembolism by reducing the body's ability to inhibit clotting.

What are the implications of Protein C and S deficiencies?

Deficiencies in Protein C and S impair the regulation of coagulation, leading to increased thrombotic events.

Explain activated protein C resistance (Factor V Leiden).

Factor V Leiden is a genetic mutation that makes coagulation factor V resistant to inactivation by activated protein C.

Describe prothrombin 20210A mutation.

This mutation increases prothrombin levels, elevating the risk of thrombus formation.

What is Factor 12 deficiency?

A rare deficiency of Factor 12, which has no major clinical consequences but can affect laboratory test results.

What defects are found in the fibrinolytic system?

Defects may lead to impaired breakdown of blood clots, increasing the risk of thrombosis.

Characterize antiphospholipid antibodies.

Antiphospholipid antibodies are autoantibodies that increase the risk of thrombosis and fetal loss.

What laboratory assays are associated with antiphospholipid syndrome?

Tests include the lupus anticoagulant test, anticardiolipin antibodies, and anti-beta-2 glycoprotein I antibodies.

Briefly describe HHT (Hereditary Hemorrhagic Telangiectasia).

HHT is a genetic condition causing abnormal blood vessel formation, leading to frequent nosebleeds and bleeding.

What is Ehlers-Danlos syndrome?

A group of genetic disorders affecting connective tissue, leading to fragile skin, joint hypermobility, and bleeding.

Define allergic purpura (HSP).

Henoch-Schonlein Purpura (HSP) is a small-vessel vasculitis characterized by purpura, usually in children.

What is senile purpura?

Age-related bruising caused by fragile skin and blood vessels in elderly individuals.

Differentiate between thrombocytopenia, thrombocytosis, thrombocythemia, and thrombocytopathy.

Thrombocytopenia is low platelet count, thrombocytosis is high platelet count, thrombocythemia is a form of thrombocytosis due to a myeloproliferative disorder, and thrombocytopathy refers to dysfunctional platelets.

Identify four general causes of thrombocytopenia.

Causes include marrow failure, hypersplenism, increased destruction, and dilutional effects.

Explain how drugs may bind to platelets immunologically.

Immunologic mechanisms involve antibodies binding to drug-modified platelets, leading to their destruction.

What are non-immunologic mechanisms of drug-induced platelet binding?

Non-immunologic binding can occur through direct interaction of drugs with platelets, altering their function.

Describe defects in storage pool disease.

Storage pool disease results from defective platelet granule release, impairing hemostasis.

What is gray platelet syndrome?

A rare bleeding disorder characterized by a deficiency of alpha granules in platelets.

List some drugs with anti-platelet actions.

Examples include aspirin, clopidogrel, and ticagrelor.

What is Immune Thrombocytopenic Purpura (ITP)?

ITP is an autoimmune disorder leading to a decrease in platelets due to antibody-mediated destruction.

Differentiate between acute and chronic ITP.

Acute ITP often occurs after infection in children, whereas chronic ITP persists in adults with varied causes.

What is immunologic drug-induced thrombocytopenia?

A condition where drugs induce an immune response resulting in a decrease in platelet count.

Define neonatal alloimmune thrombocytopenia (NAIT).

NAIT is a condition where fetal platelets are attacked by maternal antibodies, leading to low platelet counts in the newborn.

What is Thrombotic Thrombocytopenic Purpura (TTP)?

TTP is a rare disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ dysfunction.

Describe Hemolytic-Uremic Syndrome (HUS).

HUS is characterized by acute renal failure, hemolytic anemia, and thrombocytopenia, often occurring after gastrointestinal infection.

What is Heparin-Induced Thrombocytopenia (HIT)?

HIT is an immune response to heparin therapy that results in thrombocytopenia and increased risk of thrombosis.

Define Glanzmann Thrombasthenia.

A genetic disorder where platelets lack the glycoprotein IIb/IIIa complex, impairing aggregation.

What is Bernard-Soulier syndrome?

A genetic condition characterized by a deficiency of glycoprotein Ib, leading to defective platelet adhesion.

Describe May-Hegglin Anomaly.

A genetic disorder causing thrombocytopenia and large platelets, associated with Döhle body leukocytes.

Compare and contrast reasons for clotting factor deficiencies.

Reasons include genetic defects, vitamin K deficiency, liver disease, or autoimmune diseases.

Describe clinical features of hemophilia A.

Hemophilia A is characterized by excessive bleeding, especially in joints, due to Factor VIII deficiency.

What are the clinical features of hemophilia B?

Hemophilia B presents similarly to hemophilia A but is due to Factor IX deficiency.

What laboratory findings are associated with fibrinogen defects?

Laboratory findings include prolonged PT and aPTT, and low fibrinogen levels.

Describe von Willebrand disease (vWD).

vWD is a bleeding disorder caused by a deficiency or dysfunction of von Willebrand factor, leading to platelet dysfunction.

Distinguish between qualitative and quantitative clotting factor defects.

Qualitative defects involve abnormal function of clotting factors, while quantitative defects involve insufficient amounts.

What is disseminated intravascular coagulation (DIC)?

DIC is a serious condition characterized by widespread activation of the clotting cascade, leading to thrombosis and bleeding.

What are the etiologies of DIC?

Common causes include sepsis, trauma, obstetric complications, and malignancy.

Explain the pathophysiology of DIC.

DIC involves excessive coagulation leading to thrombin generation, platelet consumption, and subsequent bleeding due to factor depletion.

What are the clinical findings in DIC?

Clinical findings include bleeding, organ dysfunction, skin necrosis, and petechiae.

What laboratory test results are indicative of DIC?

Tests show thrombocytopenia, prolonged PT/aPTT, low fibrinogen, and elevated D-dimer.

What is the treatment for DIC?

Treatment involves addressing the underlying cause, transfusion of blood products, and supportive care.

Discuss inhibitors to specific coagulation factors.

Inhibitors, often antibodies, can develop against factors such as Factor VIII in hemophilia, complicating treatment.

What are the clinical implications of coagulation factor inhibitors?

They can lead to treatment resistance and require tailored therapies such as immune suppression.