Platelet Disorders and Primary Hemostasis Quiz

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Questions and Answers

What is the initial step in the primary hemostasis process following vascular injury?

Transient vasoconstriction (correct)

Platelet degranulation

Platelet aggregation

Platelet adhesion

Which factor is released by endothelial cells and plays a critical role in platelet adhesion to the vessel wall?

Thromboxane A2 (TXA2)

Fibrinogen

Von Willebrand factor (vWF) (correct)

ADP

What is the main consequence of prolonged bleeding time in patients with platelet disorders?

Improved platelet aggregation

Easier bruising and mucosal bleeding (correct)

Increased risk of thrombosis

Reduced platelet count

Which of the following is a typical clinical manifestation of mucosal bleeding associated with primary hemostasis disorders?

Hemoptysis Signup and view all the answers

What mediates the platelet aggregation during primary hemostasis?

Fibrinogen Signup and view all the answers

Which of the following laboratory tests is primarily used to assess the number and size of platelets?

Blood smear Signup and view all the answers

In the primary hemostasis process, what role does ADP play during platelet activation?

Promotes platelet aggregation Signup and view all the answers

Which bleeding symptom is specifically indicative of thrombocytopenia?

Petechiae Signup and view all the answers

What is the primary function of von Willebrand factor (vWF) in platelet aggregation?

Induces platelet aggregation Signup and view all the answers

What is the role of vitamin K in coagulation factor function?

Activates coagulation factors through gamma carboxylation Signup and view all the answers

Which of the following is a common cause of vitamin K deficiency in newborns?

Lack of GI colonization by bacteria Signup and view all the answers

What laboratory finding is best used to screen for disseminated intravascular coagulation (DIC)?

Elevated D-dimer Signup and view all the answers

How does liver failure affect coagulation?

Decreases production of coagulation factors Signup and view all the answers

What effect does radical prostatectomy have on fibrinolysis?

Activates plasmin through urokinase release Signup and view all the answers

Which of the following is considered a major risk factor for thrombosis?

Endothelial cell damage Signup and view all the answers

What is the primary treatment for disorders of fibrinolysis?

Aminocaproic acid Signup and view all the answers

What is a major result of disseminated intravascular coagulation (DIC)?

Widespread microthrombi and bleeding Signup and view all the answers

Which of the following factors is NOT gamma-carboxylated by activated vitamin K?

Factor III Signup and view all the answers

What is the primary mechanism through which heparin-induced thrombocytopenia occurs?

Platelet destruction due to heparin therapy Signup and view all the answers

How does stasis of blood flow contribute to thrombosis?

Encourages platelet activation Signup and view all the answers

What characterizes a thrombus as opposed to a postmortem clot?

Presence of lines of Zahn Signup and view all the answers

What characterizes the acute form of immune thrombocytopenic purpura (ITP)?

It usually occurs in children following a viral infection and self-resolves within weeks. Signup and view all the answers

What laboratory findings are typically present in microangiopathic hemolytic anemia?

Thrombocytopenia with normal PT and PTT. Signup and view all the answers

What is the primary treatment for chronic immune thrombocytopenic purpura (ITP) in adults?

Splenectomy. Signup and view all the answers

How does hemolytic uremic syndrome (HUS) primarily affect children?

It is commonly triggered by E coli O157:H7 infection. Signup and view all the answers

What is the mechanism of action for aspirin in the context of platelet function?

It inactivates cyclooxygenase, which leads to impaired aggregation due to lack of TXA2. Signup and view all the answers

What coagulation factor deficiency is associated with Hemophilia A?

Factor VIII. Signup and view all the answers

What characteristic distinguishes Glanzmann thrombasthenia?

Impaired platelet aggregation due to GPIIb/IIIa deficiency. Signup and view all the answers

How does a coagulation factor inhibitor present in lab tests?

Normal PT and prolonged PTT that does not improve with mixing studies. Signup and view all the answers

Which condition is characterized by a deficiency of von Willebrand factor (vWF)?

von Willebrand disease. Signup and view all the answers

What is a primary laboratory feature of secondary hemostasis disorders?

Deep tissue bleeding into joints. Signup and view all the answers

In hemophilia B (Christmas disease), which factor is deficient?

Factor IX. Signup and view all the answers

What leads to microangiopathic hemolytic anemia?

Pathologic formation of platelet microthrombi in small vessels. Signup and view all the answers

What are the expected findings on a bone marrow biopsy in ITP?

Increased megakaryocytes. Signup and view all the answers

What is the underlying issue in Bernard-Soulier syndrome?

Genetic GP Ib deficiency resulting in impaired platelet adhesion. Signup and view all the answers

What is a consequence of vitamin B12 and folate deficiency?

Decreased conversion of homocysteine to methionine Signup and view all the answers

Cystathionine beta synthase (CBS) deficiency is characterized by which of the following?

High homocysteine levels and homocystinuria Signup and view all the answers

What condition is most commonly associated with factor V Leiden mutation?

Thrombosis at a young age Signup and view all the answers

Which of the following best describes the role of C and S proteins in coagulation?

Inactivates coagulation factors V and VIII Signup and view all the answers

What is the characteristic appearance of an atherosclerotic embolus?

Presence of cholesterol clefts Signup and view all the answers

What is a common complication of warfarin therapy in patients with preexisting protein C or S deficiency?

Warfarin skin necrosis Signup and view all the answers

Which of the following embolisms is characterized by respiratory symptoms and petechiae on the skin over the chest?

Fat embolism Signup and view all the answers

In cases of pulmonary embolism (PE), which diagnostic test is most useful to detect deep vein thrombosis (DVT)?

Lower extremity Doppler ultrasound Signup and view all the answers

What condition involves nitrogen gas precipitating out of blood due to rapid ascent by a diver?

Gas embolism Signup and view all the answers

What is the clinical presentation of pulmonary embolism (PE)?

Chest pain and hemoptysis Signup and view all the answers

What are amniotic fluid emboli characterized by?

Squamous cells and keratin debris Signup and view all the answers

What leads to increased thrombin production in prothrombin 20210A mutation?

Increased gene expression of prothrombin Signup and view all the answers

Which of the following is a common symptom of systemic embolism?

Parestesia in extremities Signup and view all the answers

What factor is most commonly associated with pulmonary embolism?

Deep venous thrombus of the lower extremity Signup and view all the answers

In A Till deficiency, which of the following occurs with standard heparin dosing?

PTT does not rise Signup and view all the answers

Study Notes

Hemostasis is a crucial process for repairing damaged blood vessels, forming a clot to stop bleeding.
It's a two-stage process:
- Primary hemostasis: forms a platelet plug (weak) via platelet-vessel wall interaction.
- Secondary hemostasis: stabilizes the plug through the coagulation cascade, forming a stable clot.

Primary Hemostasis

Step 1: Transient vasoconstriction of damaged vessel, mediated by reflexes and endothelin release.
Step 2: Platelet adhesion to the disrupted vessel.
- vWF (von Willebrand factor) binds exposed collagen.
- Platelets bind vWF through GPib receptors.
- vWF is from endothelial cells and platelet α-granules.
Step 3: Platelet degranulation.
- Release of mediators (e.g., ADP, TXA2) from dense granules.
- ADP promotes GPIIb/IIIa receptor exposure on platelets.
- TXA2 (from COX) promotes aggregation.
Step 4: Platelet aggregation.
- Platelets aggregate via GPIIb/IIIa using fibrinogen as a linking molecule.
- Forms a weak platelet plug, stabilized by secondary hemostasis.

Disorders of Primary Hemostasis

Often due to platelet abnormalities (quantitative or qualitative).
Clinical features: Mucosal and skin bleeding.
- Mucousal: Epistaxis, hemoptysis, GI bleeding, hematuria, menorrhagia, intracranial bleeding with severe thrombocytopenia.
- Skin: Petechiae (1-2 mm), ecchymoses (> 3 mm), purpura (> 1 cm), easy bruising.
Laboratory studies:
- Platelet count (normal 150-400 x 10^9/L): <50 x 10^9/L leads to symptoms.
- Bleeding time (normal 2-7 minutes): Prolonged with disorders.
- Blood smear to assess platelets.
- Bone marrow biopsy to assess megakaryocytes (platelet producers).

Immune Thrombocytopenic Purpura (ITP)

Autoimmune disorder: IgG produced against platelet antigens (e.g., GPIIb/IIIa).
Most common cause of thrombocytopenia in children and adults.
Plasma cells in spleen produce antibodies.
Antibody-bound platelets consumed by splenic macrophages causing low platelet counts.
Two types:
- Acute (children; weeks after viral infections; self-limiting).
- Chronic (adults, often women; may be primary or secondary; may affect offspring).
Laboratory findings:
- Low platelet count (<50 x 10^9/L).
- Normal PT/PTT (coagulation cascade unaffected).
- Normal megakaryocytes on bone marrow biopsy.
Initial treatment: corticosteroids; IVIG for symptomatic bleeding. Splenectomy in refractory cases.

Microangiopathic Hemolytic Anemia

Pathologic platelet microthrombi in small vessels cause RBC damage (schistocytes).
Seen in TTP and HUS.
TTP: Reduced ADAMTS13 (cleaves vWF multimers).
- Large multimers cause abnormal platelet adhesion, microthrombi.
- Acquired autoantibody against ADAMTS13 is common (adult females).
HUS: Endothelial damage (drugs or infection, e.g., E. coli O157:H7).
- E. coli verotoxin damages endothelial cells, platelet microthrombi.
Clinical features (TTP and HUS):
- Skin and mucosal bleeding.
- Microangiopathic hemolytic anemia.
- Fever.
- Renal insufficiency (HUS more common).
- CNS abnormalities (TTP more common).
Laboratory findings:
- Thrombocytopenia, prolonged bleeding time.
- Normal PT/PTT.
- Anemia with schistocytes.
- Increased megakaryocytes on bone marrow biopsy.
Treatment: plasmapheresis and corticosteroids, especially in TTP.

Qualitative Platelet Disorders

Bernard-Soulier syndrome: Genetic GPib deficiency; impaired platelet adhesion.
Glanzmann thrombasthenia: Genetic GPIIb/IIIa deficiency; impaired aggregation.
Aspirin: Irreversibly inactivates cyclooxygenase, inhibiting TXA2 and aggregation.
Uremia: Disrupts platelet function; affects adhesion and aggregation.

Secondary Hemostasis

Stabilizes platelet plug by activating the coagulation cascade which generates thrombin
Thrombin converts fibrinogen in the plug to fibrin.
Fibrin is cross-linked for a stable platelet-fibrin thrombus.
Coagulation cascade factors are produced by liver in inactive forms, requiring:
- Exposure to an activating substance (tissue thromboplastin activates factor VII; subendothelial collagen activates factor XII).
- Phospholipid surface of platelets.
- Calcium.

Disorders of Secondary Hemostasis

Usually factor abnormalities.
Clinical features: Deep tissue bleeding (muscles, joints), rebleeding after procedures.
Laboratory studies:
- Prothrombin Time (PT): Measures extrinsic and common pathways.
- Partial Thromboplastin Time (PTT): Measures intrinsic and common pathways.

Hemophilia A

Genetic factor VIII deficiency (X-linked recessive).
Presents with deep tissue, joint, and post-surgical bleeding.
Severity depends on the degree of deficiency.
Laboratory findings:
- Prolonged PTT, normal PT.
- Low FVIII levels.
- Normal platelet count and bleeding time.
Treatment: recombinant FVIII.

Hemophilia B (Christmas Disease)

Genetic factor IX deficiency.
Similar to hemophilia A, but FIX levels are decreased.

Coagulation Factor Inhibitor

Acquired antibody against a coagulation factor.
Most commonly anti-FVIII.
Clinical and lab findings similar to hemophilia A.
Mixing study: PTT does not correct with normal plasma.

Von Willebrand Disease

Genetic vWF deficiency (most common inherited coagulation disorder).
Multiple subtypes (quantitative and qualitative defects; most common is decreased vWF levels).
Presents with mild mucosal and skin bleeding.
Laboratory findings:
- Prolonged bleeding time.
- Prolonged PTT (normal PT - vWF stabilizes FVIII)
- Abnormal ristocetin test (lack of vWF impairs platelet aggregation).
Treatment: desmopressin (ADH analog) to increase vWF release.

Vitamin K Deficiency

Disrupts multiple coagulation factors.
Vitamin K is activated by epoxide reductase in the liver →gamma-carboxylates factors II, VII, IX, X, and proteins C and S (necessary for function).
Deficiency is seen in:
- Newborns (due to lack of GI colonization; prophylaxis).
- Long-term antibiotic therapy (alters gut bacteria).
- Malabsorption (fat-soluble vitamin deficiency).

Other Causes of Abnormal Secondary Hemostasis

Liver failure (Decreased coagulation factor production).
Large-volume transfusion (dilutes factors).

Other Disorders of Hemostasis

Heparin-induced thrombocytopenia (HIT): Platelet destruction secondary to heparin therapy.
Disseminated Intravascular Coagulation (DIC): Pathologic coagulation cascade activation.
- Results in widespread microthrombi causing ischemic and infarct events.
- Platelet and factor consumption lead to bleeding (especially from IV sites).
- Almost always secondary to another disease (obstetric complications, sepsis, adenocarcinoma, acute promyelocytic leukemia, rattlesnake bite).
- Laboratory findings:
  - Low platelet count.
  - Increased PT/PTT.
  - Low fibrinogen.
  - Microangiopathic hemolytic anemia.
  - Elevated fibrin split products (particularly D-dimer). D-dimer is elevated with DIC and is the best test!
- Treatment: addressing underlying cause and blood product transfusions (e.g., cryoprecipitate).

Disorders of Fibrinolysis

Normal fibrinolysis removes thrombi after vessel healing.
Tissue plasminogen activator (tPA) converts plasminogen to plasmin, cleaving fibrin and blocking aggregation &activating coagulation factors.
a2-antiplasmin inactivates plasmin.
Disorders are due to plasmin overactivity.
- Examples: radical prostatectomy, cirrhosis.
- Laboratory findings:
  - Elevated PT/PTT.
  - Increased bleeding time (without thrombocytopenia).
  - Elevated fibrinogen split products (without D-dimers).
- Treatment: Aminocaproic acid (blocks plasminogen activation).

Thrombosis

Pathologic blood clot formation in blood vessel.
Common in deep leg veins (DVT).
Characterized by Lines of Zahn (alternating platelets, fibrin, RBCs) and vessel wall attachment.
Risk factors (Virchow triad):
- Disrupted blood flow (stasis/turbulence e.g. immobilization, cardiac dysfunction).
- Endothelial cell damage (atherosclerosis, vasculitis).
- Hypercoagulable state (inherited/acquired, e.g. Protein C/S def., factor V Leiden, prothrombin 20210A, ATIII def.)

Embolism

Intravascular mass occluding downstream vessels.
Thromboembolus (most common: dislodged thrombus).
Atherosclerotic embolus (from plaque).
Fat embolus (bone fractures/trauma: bone marrow elements in vessels).
Gas embolus (decompression sickness, laparoscopic surgery).
Amniotic fluid embolus (labor/delivery; squamous cells/keratin debris; DIC).

Pulmonary Embolism (PE)

Usually thromboembolus (often from DVT).
Often clinically silent (dual blood supply, small embolus).
Pulmonary infarction (large/medium embolus, pre-existing compromise).
- Symptoms: shortness of breath, hemoptysis, pleuritic chest pain, pleural effusion.
- Diagnosis: V/Q lung scan (abnormal perfusion), spiral CT (filling defect), Doppler ultrasound (DVT), elevated D-dimer.

Systemic Embolism

Usually thromboembolus from left heart.
Travel to occlude flow to organs, often lower extremities.

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Description

Test your knowledge on the initial steps of primary hemostasis and the role of platelets in the bleeding process. This quiz covers key factors that influence platelet adhesion, aggregation, and clinical manifestations of bleeding disorders. It's essential for understanding hemostatic mechanisms and their clinical implications.