Case 3

Question 1

Prothrombin Time (PT)

Answer 1

• Extrinsic pathway

* Factors involved: V, VII, X, prothrombin, and fibrinogen

Question 2

Partial Thromboplastin Time (PTT)

Answer 2

• Intrinsic pathway

* Factors involved: Everything except VII and XIII

Question 3

What causes secondary hemostasis disorders?

Answer 3

Failure to clot

Question 4

Which disorders are secondary hemostasis disorders? (4)

Answer 4

1. Hemophilia A
2. Hemophilia B
3. Vitamin K Deficiency
4. Liver failure

Question 5

What are some general characteristics and manifestations of platelet disorders?

Answer 5

• PT and PTT not affected
• Bleeding time is increased
• Manifestations: mucosal & skin bleeding

Question 6

Which disorders are functional platelet disorders? (3)

Answer 6

1. Bernard-Soulier Disease
2. Glanzmann thrombasthenia
3. Ureamia

Question 7

Which disorders are platelet number disorders? (4)

Answer 7

1. Idiopathic thrombocytopenic purpura (ITP)
2. Thrombotic thrombocytopenic purpura (TTP)
3. Hemolytic uremic syndrome (HUS)
4. Heparin-induced Thrombocytopenia (HIT)

Question 8

What are some general characteristics of secondary hemostasis disorders?

Answer 8

• Due to factor abnormalities
• Deep tissue bleeding into muscles and joints
• Rebleeding after surgical procedures

Question 9

Hemophilia A*

Answer 9

• Factor VIII deficiency
• X-linked recessive (men affected)
• Sx: asymptomatic, easily bruised, excessive bleeding
• Labs: ↑ PTT, normal PT
• Tx: Factor replacement therapy, DDADP (desmopression), EACA

Question 10

Hemophilia B (aka Christmas Disease)

Answer 10

• Factor IX deficiency
• X-linked recessive (men affected)
• Sx: asymptomatic, easily bruised, excessive bleeding
• Labs: ↑ PTT, normal PT

Question 11

Vitamin K Deficiency*

Answer 11

• Activation of coagulation factors II, VII, IX, X, Protein C & S
• Labs: ↑ PTT & PT
• Tx: Vitamin K Supplement & treatment of coagulopathy

Question 12

Liver failure (cirrhosis)

Answer 12

↓ coagulation factors, ↓ Vitamin K, ultrasound shows shrunken, nodular liver

Question 13

Bernard-Soulier Disease

Answer 13

• Defective platelet plug formation due to decreased Gp1b (adhesion affected)
• Labs: low # of platelets but enlarged platelets
• Tx: transfusion of normal platelets

Question 14

Glanzmann thrombasthenia

Answer 14

• Defective platelet plug formation due to decreased GpIIb/IIIa (aggregation affected)

Question 15

Ureamia

Answer 15

• Disrupts both adhesion and aggregation of platelets

Question 16

Idiopathic thrombocytopenic purpura (ITP)*

Answer 16

• Spleen makes antibodies (IgG) against platelet antigens → destruction of platelets by macrophages in spleen
• Primary or secondary due to HIV or SLE
• Sx: bruising, petechiae, epistaxis
• Labs: ↓ Platelets (<20k), normal PT and PTT, ↑ megakaryocytes
• Tx: corticosteroids, IVIG, anti-D immunoglobulin, Rituximab, Romiplostim & Eltrombopag, TPO-mimetic agents (only ones that stimulate platelet production, others prevent destruction)

Question 17

Thrombotic thrombocytopenic purpura (TTP)

Answer 17

• Caused by genetics, medications or autoimmune
• Sx: the “pentrad” = thrombocytopenic purpura, fever, renal failure, neurological changes and microangiopathic hemolytic anemia
• Labs: normal PT and PTT, ↑ bleeding time, ↑ megakaryocytes
o Smear shows few platelets, schistocytes

Question 18

Hemolytic uremic syndrome (HUS)

Answer 18

• Mostly in kids after gastroenteritis w/ bloody diarrhea.

* Sx: triad = thrombocytopenic purpura, renal failure and microangiopathic hemolytic anemia

Question 19

Heparin-induced Thrombocytopenia (HIT)

Answer 19

• Auto-immune
• May be fatal
• Tx: discontinue Heparin + a direct thrombin inhibitor

Question 20

Which disorders are mixed platelet and coagulation disorders? (2)

Answer 20

1. Von Willebrand Disease

2. DIC (disseminated intravascular coagulation)

Question 21

Von Willebrand Disease

Answer 21

• Defective platelet plug formation due to a defect in quantity or quality of von Willibrand factor (VWF) → defect in platelet plug → bleeding
• Autosomal dominant
• Sx: mild mucosal bleeding
• Labs: ↑ bleeding time, ↑ PTT (due to VIII affected)
• Tx: desmopressin

Question 22

DIC (disseminated intravascular coagulation)

Answer 22

• Clotting factor and platelet problem
• Causes: amniotic fluid embolism, infections, cancer, & major traumas, particularly head injuries
• Labs: ↓ platelets, ↓ fibrinogen, ↑ bleeding time, ↑ PT, ↑ PTT, ↑ D dimer & schistocytes on smear
• Tx: treat underlying cause, administer platelet and fresh frozen plasma as needed, & Heparin

Question 23

Which disorders are hereditary thrombosis syndromes? (4)

Answer 23

1. Proteins C and S Deficiency
2. Factor V Leiden Deficiency
3. Prothrombin Gene Mutation
4. Antithrombin III Deficiency

Question 24

Proteins C and S Deficiency

Answer 24

Results in the inability to inactivate factors V and VIII → increased risk of DVT & pulmonary embolism, cerebral venous thrombosis and warfarin-induced skin necrosis

Question 25

Factor V Leiden Deficiency

Answer 25

* Most common risk factor for DVT and PE in caucasians * Labs: ↑ PTT & PT * Tx: Heparin then Warfarin

Question 26

Prothrombin Gene Mutation

Answer 26

Mutation in 3’ untranslated region → increase in circulating thrombin and venous clots

Question 27

Antithrombin III Deficiency

Answer 27

* AT-III is a potent inhibitor of clotting cascade. Deficiency → increased venous clots * Heparin administration does nothing!

Question 28

Which drugs are thrombolytic drugs? (3)

Answer 28

1. Tissue-type plasminogen activator, alteplase 2. Reteplase 3. Streptokinase

Question 29

Unfractionated heparin

Answer 29

* Indirect thrombin inhibitor | * Mixture of highly electronegative acidic mucopolysaccharides w/ high MW

Question 30

Enoxaparin

Answer 30

* Indirect thrombin inhibitor * Low MW heparin * SC 2x/day

Question 31

Fondaparinux

Answer 31

* Indirect thrombin inhibitor * Synthetic analog of heparin * SC once/day

Question 32

Heparin

Answer 32

* Indirect thrombin inhibitor * MOA: binds AT-III and inactivates thrombin factors IXa, Xa and XIIa * Short half-life * Use PTT to monitor * SE: hemorrhage, HIT, osteoporosis & fractures

Question 33

Warfarin

Answer 33

* Oral anticoagulant * Use PT to monitor * Inhibits synthesis of Vit K dependent clotting factors II, VII, IX & X * SE: bleeding risk, teratogenic, tissue skin necrosis

Question 34

Tell me more about thrombolytic drugs

Answer 34

* Clot busters * MOA: binds to and converts plasminogen to plasmin * Indications: MI, DVT, PE, ischemic stroke (t-PA) * Contra: active bleeding, history of intracranial bleeding, recent surgery, & HTN * SE: cerebral hemorrhage, severe bleeding & cholesterol embolism

Question 35

Which drugs are direct thrombin inhibitors? (4)

Answer 35

1. Lepirudin 2. Bivalirudin 3. Argatroban 4. Dabigatran

Question 36

COX Inhibitors

Answer 36

* Antiplatelet drugs * MOA: inhibit TXA2 mediated platelet aggregation * Ex: Aspirin

Question 37

ADP Antagonists

Answer 37

* Antiplatelet drugs * MOA: inhibits ADP-mediated platelet aggregation * Ex: Ticlopidine & Clopidogrel

Question 38

Glycoprotein IIb/IIIa Inhibitors

Answer 38

* Antiplatelet drugs * MOA: inhibits binding of fibrinogen to platelet GpIIb/IIIa, preventing platelet cross-linking * Ex: Abciximab

Question 39

What are the 3 vaccines you need to give before a splenectomy?

Answer 39

1. H. influenza B 2. Pneumococci 3. Meningococci

Question 40

What are the Vitamin K dependent clotting factors? (6)

Answer 40

II, VII, IX, X, protein C & protein S

Question 41

Deep Venous Thrombosis (DVT)*

Answer 41

* Unilateral swelling in LE * Virchow's Triad are risk factors * Ddx: cellulitis, superficial thrombophlebitis, chronic venous valvular insufficiency, ruptured Baker's cyst * Sx: swelling & redness in leg * Labs: venous doppler * Tx: Heparin

Question 42

Virchow's Triad

Answer 42

1. Alteration in blood flow (ex: stasis) 2. Vascular endothelial injury 3. Alterations in the constituents of the blood (ex: inherited or acquired hypercoagulable state)

Question 43

What are the most common genetic risk factors for DVT? (5)

Answer 43

1. Factor V Leiden Mutation 2. Prothrombin Gene Mutation 3. Protein S Deficiency 4. Protein C Deficiency 5. Antithrombin Deficiency