Exam 1 I am tired and sad and running out of hope Flashcards
Define Hemostasis
Stopping blood flow with a fine balance between bleeding and clotting
What parameters are involved in hemostasis?
Vacular, platelets, fibrin clot formation - coagulation cascade, control (inhibitory systems), fibrinolysis
Procoagulant - what are things that participate in coagulation?
Platelets, vWF, coagulation factors, collagen
What does a deficiency in procoagulants result in?
BLEEDING
(except XII, Ia, PK, HMWK dysfunction)
Anticoagulant - what are things that participate in the regulation or inhibition of coagulation?
Antithrombin, Protein C, Protein S, HC II, Protein Z/ZPI, TFPI
What is the function of antithrombin?
Inactivates IIa, Xa, (IXa, XIa, XIIa, plasmin)
What is the function of Protein C?
Inactivates thrombin and thrombomodulin
What activates Protein C?
Thrombin and thrombomodulin
What is the function of Protein S?
In its free form, it is a Protein C cofactor
What is the function of HCII?
It neutralizes IIa (thrombin)
What is the function of TFPI?
Inhibits TF3/VIIa complex
What does a deficiency in anticoagulants result in?
THROMBOSIS
Profibrinolytic - what are things that participate in fibrinolysis?
Plasminogen (to plasmin), tPA, Factor XIIa, Kallikren, Urokinase
What is the function of Plasminogen (to plasmin)?
Lyses fibrin and fibrinogen and inactivates Va, VIIIa, and XIIa
What is the function of tPA?
Catalyzes the conversion of plasminogen to plasmin
What is the function of kallikren?
Formation and release of bradykinin
What is the function of urokinase?
Enzyme that converts plasminogen to plasmin
What does a deficiency in profibrinolytics result in?
THROMBOSIS
Antifibrinolytic - what are things that participate in the regulation or inhibition of fibrinolysis?
PAI-1 & 2, Alpha-2 Antiplasmin, Alpha-2 Macroglobulin, TAFI, Factor XIa
What is the function of PAI-1 & 2?
Neutralize tPA
What is the function of Alpha-2 Antiplasmin?
Binds plasmin
What is the function of Alpha-2 Macroglobulin?
Binds plasmin
What is the function of TAFI?
Alters the fibrin clot so that it is less recognizable by plasmin
What is the function of XIa?
Enhances TAFI production
What does a deficiency in antifibrinolytics result in?
BLEEDING
What is the difference between FDP and D-Dimer?
D-Dimer is a specific FDP only present upon the degradation of a cross linked fibrin.
Factor 13 has stabilized the clot
FDP stands for what? What are FDPs?
Fibrinogen Degradation Products
Fragments X, Y, D, and E are FDPs
What are primary fibrinolysis intermediates?
X and Y
What are primary fibrinolysis end products?
D and E
T/F: FDPs can act as coagulation inhibitors by attaching to fibrin monomer and preventing polymerization and clot formation
TRUE
Function of anticoagulants?
Inhibit the coagulation cascade
What anticoagulants are we concerned with?
Coumadin/Warfarin
Heparin
Direct Thrombin Inhibitors
Direct Xa inhibitors
Mechanism of Coumadin/Warfarin
Keeps Vitamin K in storage form
Stops Vitamin K dependent factors (II, VII, IX, and X)
Mechanism of Heparin
Increase inhibitory effect of AT which creates an irreversible complex with IIa, IXa, Xa, XIa, XIIa, and plasmin
Mechanism of Direct Thrombin Inhibitors
Neutralizes thrombin by binding to the active site and extending fibrin bound thrombin
Mechanism of Direct Xa inhibitors
Inhibits Factor Xa (no AT requires)
Function of Anti-Platelets
Prevents platelet aggregation
What drug that we are concerned with is an anti-platelet?
Aspirin
Mechanism of Aspirin
Inhibits cyclooxygenase to reduce TXA2 production (which stimulates activation of new platelets and increases aggregation)
Mechanism of thrombolytics (Fibrin specific or fibrin non-specific)
Dissolves the clot
What is the type of disorder, defect, and laboratory results we would see in Von Willebrands (Type 1)
Disorder: Adhesion
Defect: vWF deficiency (all multimers)
Tests:
PFA = INC
PT = normal
APTT = INC (d/t DEC VIII_
PLT Aggregation = abnormal Ristocetin (will correct with addition of NP)
What is the type of disorder, defect, and laboratory results we would see in Bernard-Soulier
Disorder: Adhesion
Defect: Lack of Gp1b
Tests:
PFA = INC
PLT = DEC
Large PLT
PLT Aggregation = abnormal Ristocetin
What is the type of disorder, defect, and laboratory results we would see in Glanzmann’s
Disorder: Aggregation
Defect: Lack GPIIb and GPIIIa
Tests:
PFA = INC
PT = normal
APTT = normal
PLT count = normal
PLT aggregation = normal ONLY w/Ristocetin
What is the type of disorder, defect, and laboratory results we would see in Delta Storage Pool
Disorder: Release
Defect: Lack of dense granules
Tests:
Hypo or granular plts
What is the type of disorder, defect, and laboratory results we would see in Gray Platelet
Disorder: Release
Defect: Marked DEC in platelet alpha granules
Tests:
Hypo or granular plts
What is the type of disorder, defect, and laboratory results we would see in ITP
Disorder: Thrombocytopenia
Defect: Spontaneous – adults/AIDS; kids/immunization
Tests:
PFA = INC
PLT count = LOW <20,000
Large plt (variable)
BM = megakaryocyte hyperplasia
Deficient clot retraction
What is the type of disorder, defect, and laboratory results we would see in TTP
Disorder: Thrombocytopenia
Defect: Autoantibody against ADAMTS13, vWF cannot break apart
Tests:
- Hemolytic anemia with schistocytes
- Thrombocytopenia/hemorrhage
- Fluctuating neurological dysfunction
- Fever
- Progressive renal disease
What is the type of disorder, defect, and laboratory results we would see in HUS
Disorder: Thrombocytopenia
Defect: Resembles TTP with NO neurologic symptoms. Plts are sequestered in kidney
Tests:
- MAHA
- thrombocytopenia
- acute renal failure (RBCs, protein, and casts in urine)
What is the type of disorder, defect, and laboratory results we would see in HELLP
Disorder: Thrombocytopenia
Defect: Release of TXA2. Microvascular endothelial damage. Vascular lesions. Intravascular plt activation
Tests:
- Hemolysis: hgb/hct, LDH, bili, Hapt, schisto
- PLT count = LOW <200,000
- Hepatic dysfunction (AST >42, ALT >24, LDH >164)
What is the type of disorder, defect, and laboratory results we would see in drug induced thrombocytopenia
Disorder: thrombocytopenia
Defect: Antibody complex attaches to platelet
Tests:
- Plt count LOW
- Test for the presence of heparin-induced ab in the patient plasma (use a plt aggregometer; if ab is present, plts will aggregate)
What is the site of formation of the coagulation factors?
Liver
List the Vitamin K dependent factors
II, VII, IX, and X
Factor I
Fibrinogen
Clot formation
Factor II
Prothrombin
Activation of factors I, V, VII, VIII, XI, XIII, Protein C, and platelets
Factor III
Tissue factor III
Cofactor of VIIa
Factor IV
Calcium
Role in binding of phospholipid coagulation factors
Factor V
Labile Factor
Cofactor of X – prothrombinase complex
Factor VII
Proconvertin
Enables factors IX and X
Factor VIII
von Willebrand Factor Complex
Cofactor of IX complex
Factor IX
Christmas Factor
Forms the complex with VIII; Enables factor X
Factor X
Stuart-Prower Factor
Forms the prothrombinase complex together with Factor V, which will activate Factor II
Factor XI
Activates factor IX
Factor XII
Hageman Factor
Enables factors XI, VII, and Prekallikrein
Factor XIII
Fibrin Stabilizing Factor
Creates cross-links between fibrin monomers
How does Waldenstrom’s macroglobulinemia and multiple myeloma can cause bleeding tendencies?
Igs coating platelets and collagen fibers
How does the following vascular disorder effect coagulation: hereditary hemorrhagic telangiectasia
- Vessel walls are reduced to single layer of EC and inadequate support structures resulting in fragile vessels
- Telangiectasias: Dilated superficial vessels that will blanche (lose color with pressure, unlike petechiae
- Bleeding
How does the following vascular disorder effect coagulation: Ehlers-Danlos Syndrome
- Indian rubber man (hypermobile joints and stretchy skin)
- Collagen disorder: Issues with adhesion
How does the following vascular disorder effect coagulation: Allergic and drug-induced purpura
- Autoimmune vacular injury
- Drug causes development of antibody to vessel walls
How does the following vascular disorder effect coagulation: Henoch-schonlein purpura
- Usually a child following upper respiratory infection
- IgA deposits in vessels: Rash, abdominal pain, joint pain, proteinuria/hematuria. Small % advance to renal disease
How does the following vascular disorder effect coagulation: Scurvy
- Vitamin C deficiency
- Decreased synthesis of collagen results in weakened capillary walls
How does the following vascular disorder effect coagulation: Senile Purpura
- Elderly
- Usually forearms and back of hands
- Loss of collagen and subcutaneous fat/elastic fibers to support for small blood vessels
Common agonist or aggregating agent of von willebrands
Ristocetin - corrects with NP
Common agonist or aggregating agent of bernard soulier
Ristocetin
Common agonist or aggregating agent of Glanzmann’s Thrombasthenia
All abnormal except ristocetin
Common agonist or aggregating agent of Delta storage pool disease
ADP
Common agonist or aggregating agent of Gray platelet
ADP
Common agonist or aggregating agent of Aspirin or NSAID therapy
Arachidonic acid curve = more sensitive
von Willebrand factor activity– Ristocetin co-factor (vWF: RCo) – Ristocetin Induced Platelet Agglutination
Uses patient PRP - patient’s own platelets and plasma
Normal with all agents except Ristocetin
Add NP and it will correct for VWD
von Willebrand factor activity– Ristocetin co-factor (vWF: RCo) – Ristocetin Cofactor (vWF:Rco)
Uses patient’s plasma and donor or lyophilized platelets
Measures the ability of patient’s plasma cWF to agglutinate donor platelets in the presence of Ristocetin
