HEMA Chapter 42 (Reading Assignment)

A collection of flashcards covering key concepts related to laboratory findings and their implications in thrombotic disorders, as discussed in the lecture notes.

Type 2 variants, with loss of high molecular weight multimers.

What laboratory abnormalities are often observed in AVWS?

Gastrointestinal bleeding, especially in high shear conditions like aortic stenosis

What are common bleeding events associated with AVWS?

Aortic stenosis can lead to gastrointestinal bleeding due to vWF's role, and surgical repair can correct bleeding.

What is the relationship between aortic stenosis and AVWS?

Patients with myeloproliferative neoplasms (MPNs).

In which patients is AVWS often observed?

Deficiency in ADAMTS13 leads to accumulation of large vWF multimers causing thrombosis.

What is the significance of ADAMTS13 in TTP?

Congenital TTP presents with less severe kidney injury than acquired forms.

How does congenital TTP typically present compared to acquired TTP?

Thrombocytopenia and microangiopathic hemolytic anemia.

What are the symptoms of TTP?

TFPI inhibits the TF-VIIa complex to limit coagulation activity.

What role does TFPI play in coagulation?

It neutralizes thrombin and factor Xa, enhancing through glycosaminoglycans.

What is Antithrombin and its function?

It inactivates factors Va and VIIIa, thereby reducing thrombin and fibrin formation.

What does the Protein C–Protein S system do?

It is an anticoagulant protein that requires protein S as a cofactor to function.

What is the function of activated protein C (APC)?

• Type I (quantitative)

• Type II (qualitative)

• Type III (selective deficiency of free protein S).

What are the three types of protein S deficiency?

Supports a diagnosis of TTP

What does a low level of ADAMTS13 suggest?

DNA-based genotyping

What is required for a definitive diagnosis of Factor V Leiden?

4%.

What percentage of individuals of European ancestry carry the Factor V Leiden mutation?

To measure how quickly a clot dissolves

What are euglobulin clot lysis tests used for?

Increased risk of venous thrombosis and higher plasma prothrombin levels

What is the effect of high levels of prothrombin G20210A variant?

Reduces total plasma TFPI concentration and activity.

What impact do oral contraceptives have on TFPI levels?

• Venous thromboembolism

• Neonatal purpura

• Warfarin-induced skin necrosis.

How does protein C deficiency present clinically?

In patients with VTE and relevant family history, recurrent VTE, or VTE at unusual sites.

When should thrombophilia testing be conducted?

Failure to prolong clotting time with added APC, often due to Factor V Leiden.

What is meant by activated protein C resistance?

They interfere with normal clotting, leading to thrombosis.

What is the significance of lupus anticoagulants in APS?

When ADAMTS13 is deficient or inhibited.

When might thrombin activity be diminished?

• Oral contraceptives, DIC

• Vitamin K deficiency

• Nephrotic syndrome

What conditions may result in acquired protein S deficiency?

Higher risk of major bleeding and thrombotic events

What are the clinical implications of dysfibrinogenemia?

Clotting activity assays using snake venom and antigen level assays

What tests are used to diagnose Protein C deficiency?

ADAMTS13 testing level

What laboratory feature aids in distinguishing TTP from HUS?

Increased risk of thrombosis

What does significant elevation of coagulation factor levels signify?

They provide real-time assessment of clot formation and breakdown.

How do viscoelastic tests help in thrombosis assessment?

Factor V Leiden mutation

What is the most common inherited thrombophilia?

A specific mutation that increases clotting activity by eightfold.

What is the mutation involved in the Factor IX Padua variant?

Interactions with acute-phase reactants can alter measured levels.

What challenges exist in diagnosing congenital Protein S deficiency?

It helps assess risk for thrombosis

What is the clinical utility of measuring plasma levels of homocysteine?

It may contribute to increased thrombotic risk in antiphospholipid syndrome

How does anti-TFPI activity relate to thrombosis risk?

Cancer, obesity, immobility, and use of oral contraceptives

What are common conditions associated with increased thrombotic risk?

They have thrombo regulatory roles, affecting clot formation and fibrinolysis.

What is the role of annexins A2 and A5 in thrombosis?

Reduced fibrinolytic activity can lead to increased risk of blood clot formation.

How does hypofibrinolysis affect thrombosis risk?

A prolonged clotting time that does not correct with mixing studies.

What is a characteristic feature of aPTT tests in patients with APS?

False positives or negatives

What effect do anticoagulants have on laboratory test results?

Deep venous thrombosis and risk for pregnancy complications.

What findings are typically seen in congenital antithrombin deficiency?

It is the main target of APS antibodies linked to thrombosis.

What is the clinical significance of the B2GPI protein in APS?

Diagnosis of TTP

What is indicated by levels of ADAMTS13 below 10%?

Thrombocytopenia and symptoms of microangiopathic hemolytic anemia.

What is the primary clinical presentation of TTP?

Testing for neutralizing antibodies against ADAMTS13.

What testing is critical for acquired TTP diagnoses?

The clotting activity associated with fibrin formation

What compound is measured to assess protein C function?

They have been linked to increased thrombotic risk, with higher factor levels correlating with greater risk.

How do factors VIII and IX elevations affect thrombosis risk?

They have reduced litter sizes and fetal weights due to placental thrombosis.

How do transgenic annexin A5-null mice demonstrate the role of annexin A5 in thrombosis?

It is used to detect the presence of lupus anticoagulants.

What role does the aPTT have in assessing APS?

It provides a negative feedback mechanism to dampen the coagulation process.

How is the tissue factor pathway inhibitor (TFPI) beneficial in coagulation?

Less severe kidney injury compared to those with acquired TTP.

What characterizes patients with congenital TTP?

Conditions like liver disease and infection can cause acquired deficiencies.

How do acquired conditions impact protein C levels?

Measurement of ADAMTS13 levels.

What is essential for differential diagnosis between TTP and aHUS?

Testing for known genetic mutations such as Factor V Leiden.

What is the first-line genetic evaluation for thrombophilia?

They may produce variants of unknown significance affecting clinical management.

What potential issues arise from genetic mutations of proteins involved in coagulation?

It inhibits coagulation factors Va and VIIIa to reduce thrombin generation.

What is the role of the Protein C–Protein S system in coagulation?

Antiphospholipid syndrome

What condition might elevate risk for thrombosis due to autoimmune mechanisms?

It shows promise in blocking thrombus formation in clinical trials.

What is significant about the Kaplacizumab drug for TTP treatment?

It indicates potential genetic risk and may warrant testing.

What does a family history of VTE suggest regarding thrombophilia testing?

Testing immediately after an acute thrombotic event can lead to inaccurate results.

Why is timing critical when performing thrombophilia testing?

Increased risk of thrombotic events.

What condition is associated with elevated homocysteine levels?

Heterozygous carriers of the Factor V Leiden mutation

What genetic factor significantly increases the risk of thrombosis in carriers?