Case 3 Flashcards
* = dx of one of the cases
Prothrombin Time (PT)
- Extrinsic pathway
* Factors involved: V, VII, X, prothrombin, and fibrinogen
Partial Thromboplastin Time (PTT)
- Intrinsic pathway
* Factors involved: Everything except VII and XIII
What causes secondary hemostasis disorders?
Failure to clot
Which disorders are secondary hemostasis disorders? (4)
- Hemophilia A
- Hemophilia B
- Vitamin K Deficiency
- Liver failure
What are some general characteristics and manifestations of platelet disorders?
- PT and PTT not affected
- Bleeding time is increased
- Manifestations: mucosal & skin bleeding
Which disorders are functional platelet disorders? (3)
- Bernard-Soulier Disease
- Glanzmann thrombasthenia
- Ureamia
Which disorders are platelet number disorders? (4)
- Idiopathic thrombocytopenic purpura (ITP)
- Thrombotic thrombocytopenic purpura (TTP)
- Hemolytic uremic syndrome (HUS)
- Heparin-induced Thrombocytopenia (HIT)
What are some general characteristics of secondary hemostasis disorders?
- Due to factor abnormalities
- Deep tissue bleeding into muscles and joints
- Rebleeding after surgical procedures
Hemophilia A*
- 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
Hemophilia B (aka Christmas Disease)
- Factor IX deficiency
- X-linked recessive (men affected)
- Sx: asymptomatic, easily bruised, excessive bleeding
- Labs: ↑ PTT, normal PT
Vitamin K Deficiency*
- Activation of coagulation factors II, VII, IX, X, Protein C & S
- Labs: ↑ PTT & PT
- Tx: Vitamin K Supplement & treatment of coagulopathy
Liver failure (cirrhosis)
↓ coagulation factors, ↓ Vitamin K, ultrasound shows shrunken, nodular liver
Bernard-Soulier Disease
- Defective platelet plug formation due to decreased Gp1b (adhesion affected)
- Labs: low # of platelets but enlarged platelets
- Tx: transfusion of normal platelets
Glanzmann thrombasthenia
• Defective platelet plug formation due to decreased GpIIb/IIIa (aggregation affected)
Ureamia
• Disrupts both adhesion and aggregation of platelets
Idiopathic thrombocytopenic purpura (ITP)*
- 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)
Thrombotic thrombocytopenic purpura (TTP)
• 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
Hemolytic uremic syndrome (HUS)
- Mostly in kids after gastroenteritis w/ bloody diarrhea.
* Sx: triad = thrombocytopenic purpura, renal failure and microangiopathic hemolytic anemia
Heparin-induced Thrombocytopenia (HIT)
- Auto-immune
- May be fatal
- Tx: discontinue Heparin + a direct thrombin inhibitor
Which disorders are mixed platelet and coagulation disorders? (2)
- Von Willebrand Disease
2. DIC (disseminated intravascular coagulation)
Von Willebrand Disease
- 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
DIC (disseminated intravascular coagulation)
- 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
Which disorders are hereditary thrombosis syndromes? (4)
- Proteins C and S Deficiency
- Factor V Leiden Deficiency
- Prothrombin Gene Mutation
- Antithrombin III Deficiency
Proteins C and S Deficiency
Results in the inability to inactivate factors V and VIII → increased risk of DVT & pulmonary embolism, cerebral venous thrombosis and warfarin-induced skin necrosis
Factor V Leiden Deficiency
- Most common risk factor for DVT and PE in caucasians
- Labs: ↑ PTT & PT
- Tx: Heparin then Warfarin
Prothrombin Gene Mutation
Mutation in 3’ untranslated region → increase in circulating thrombin and venous clots
Antithrombin III Deficiency
- AT-III is a potent inhibitor of clotting cascade. Deficiency → increased venous clots
- Heparin administration does nothing!
Which drugs are thrombolytic drugs? (3)
- Tissue-type plasminogen activator, alteplase
- Reteplase
- Streptokinase
Unfractionated heparin
- Indirect thrombin inhibitor
* Mixture of highly electronegative acidic mucopolysaccharides w/ high MW
Enoxaparin
- Indirect thrombin inhibitor
- Low MW heparin
- SC 2x/day
Fondaparinux
- Indirect thrombin inhibitor
- Synthetic analog of heparin
- SC once/day
Heparin
- 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
Warfarin
- 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
Tell me more about thrombolytic drugs
- 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
Which drugs are direct thrombin inhibitors? (4)
- Lepirudin
- Bivalirudin
- Argatroban
- Dabigatran
COX Inhibitors
- Antiplatelet drugs
- MOA: inhibit TXA2 mediated platelet aggregation
- Ex: Aspirin
ADP Antagonists
- Antiplatelet drugs
- MOA: inhibits ADP-mediated platelet aggregation
- Ex: Ticlopidine & Clopidogrel
Glycoprotein IIb/IIIa Inhibitors
- Antiplatelet drugs
- MOA: inhibits binding of fibrinogen to platelet GpIIb/IIIa, preventing platelet cross-linking
- Ex: Abciximab
What are the 3 vaccines you need to give before a splenectomy?
- H. influenza B
- Pneumococci
- Meningococci
What are the Vitamin K dependent clotting factors? (6)
II, VII, IX, X, protein C & protein S
Deep Venous Thrombosis (DVT)*
- 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
Virchow’s Triad
- Alteration in blood flow (ex: stasis)
- Vascular endothelial injury
- Alterations in the constituents of the blood (ex: inherited or acquired hypercoagulable state)
What are the most common genetic risk factors for DVT? (5)
- Factor V Leiden Mutation
- Prothrombin Gene Mutation
- Protein S Deficiency
- Protein C Deficiency
- Antithrombin Deficiency
