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44 Cards in this Set

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What are the producers of von Willebrand Factor?
1. Endothelial Cells
2. Megakaryocytes

**large multimers are cleaved by vWF cleaving protease (ADAMTS 13)
What are the 2 functions of vWF?
1. Platelet Adhesion = links collagen and Platelets (platelets bind to vWF via GP Ib)

2. Stabilizes Factor 8 = non-covalent linkage prolongs Factor 8 half-life from 2.4 h to 12 h
What happens to Factor 8 if there is vWF deficiency?
Factor 8 decreases b/c vWF stabilizes Factor 8 and prolongs its half-life
Explain the 2 laboratory measurements of vWF
1. Immunological assay = measures the total # of circulating molecules = quantity

2. Ristocetin Cofactor Activity = potentiates the binding of vWF to platelets = Functional assay (Qualitative)
This is the most common hereditary bleeding disorder
von Willebrand disease
What are the 2 Quantitative defects in von Willebrand Disease?
Type 1 = Autosomal dominant = mild deficiency

Type 3 = Autosomal recessive = Severe deficiency
Describe Type 2A von Willebrand Disease
Lack of larger (more active) multimers = lack of intermediate multimers = vWF is less active than it should be = Platelet Adhesion defect = Bleeding
Describe Type 2B von Willebrand Disease
Gain of function mutation in which vWF has an increased affinity for platelet GP-Ib
-causes small clots to occur all over the body
-takes both Platelets and vWF out of circulation = low levels of both = Bleeding
What are the lab findings in von Willebrand Disease?
1. Prolong Bleeding Time / PFA = b/c of defect in platelet adhesion

2. Normal platelet count, PT, PTT

3. ↓ vWF
-could be a secondary decrease in Factor 8
What type are most cases of von Willebrand disease?
Type 1 with mild or no bleeding
What is the treatment of choice for Type 1 vWF disease?
DDAVP = synthetic analog of Vasopressin --> increases the release of vWF from Endothelial cells
What is the treatment of choice for Type 2 vWF disease?
vWF replacement

**DDAVP would not work b/c you would just be releasing more non-functional vWF
What is the deficiency in Hemophilia A?
Factor 8 = Intrinsic Pathway
What is the cause of Hemophilia A?
X-linked recessive disease causing deficiency of Factor 8
-inversions, deletions, nonsense mutations, splicing errors
What gender is more commonly affected by Hemophilia A and why?
Males b/c it is an X-linked recessive disease
What are 30% of cases of Hemophilia A due to?
New mutations

**rarely cases are due to a functional defect, most are due to deficiency
What are the lab findings associated with Hemophilia A?
1. Prolonged PTT = Factor 8 = Intrinsic pathway

2. Normal Platelet count, BT/PFA, PT

3. Low Factor 8 levels
List the percents of normal Factor 8 that produce:
1. Severe hemophilia A
2. Moderate
3. Mild
1. < 1%
2. 2-5%
3. 6-50%
What product can you not form in Hemophilia A?
Fibrin clot = Secondary Hemostasis = Coagulation cascade
This is the most common inherited bleeding disorder associated with SERIOUS BLEEDING
Hemophilia A
Describe the clinical findings associated with Hemophilia A
1. Massive hemorrhage after trauma
2. Easy bruising
3. HEMARTHROSIS

**petechiae are not usually present -> those are usually due to Primary Hemostasis disorders (Platelet or vWF disorders)
What is the treatment for Hemophilia A?
Recombinant Factor 8 replacement
What is the complication with Recombinant Factor 8 replacement therapy in Hemophilia A? What is teh solution?
15% produce Anti-Factor 8 Ab's

Give Recombinant Factor 7a = if you give excess 7a you can activate the common pathway
What is the deficiency in Hemophilia B?
Factor 9 = Intrinsic Pathway

**same as Hemophilia A except that Factor 9 is deficient and is much less common
What are the lab findings for Hemophilia B?
1. Prolonged PTT

2. Low factor 9 level
What is the treatment for Hemophilia B?
Recombinant Factor 9 Replacement therapy
Why would Liver Disease be considered an acquired Coagulation Factor deficiency?
Liver produces all Coagulation Factors except vWF
What are the Lab findings in Coagulopathy of Liver Disease?
1. Prolonged PT/PTT
2. Normal Platelet count; BT/PFA
What factors are dependent on Vitamin K?
2, 7, 9, 10, Protein C & S
Vitamin K deficiency would casue deficiency of what factors?
2
7
9
10
Protein C and S
What would be the lab findings in Vitamin K deficiency?
1. Prolonged PT/PTT

2. normal platelet count; BT/PFA
What causes a deficient Vitamin K deficient state?
Warfarin = inhibits Vitamin K Epoxide Reductase
What Factor is most sensitive to Warfarin and there is the best indicator of Warfarin Anticoagulation?
Factor 7 = Extrinsic Pathway = PT

**EX-PaTriot goes to WARfarin
Describe the pathogenesis of Disseminated Intravascular Coagulation
1. Injury causes release of Tissue Factor which starts Coagulation Cascade (activates Factor 7)
2. Coagulation cause intravascular thrombosis in the microcirculation
3. Consumption of coagulation factors and platelets
4. Combo of the activation of fibrinolysis and lack of platelets due to consumption can cause bleeding
Why are Schistocytes produced in DIC?
Vascular occlusion by microthrombi causes Microangiopathic Hemolytic Anemia
What are the lab findings in DIC?
1. Prolonged PT/PTT = clotting factors have been consumed by microthrombi
2. ↑ fibrin split products, D-dimers = due to activation of Fibrinolysis
3. ↓ coagulation factor levels = due to consumption by microthrombi
4. Thrombocytopenia = due to consumption by microthrombi
5. Schistocytes
What are the clinical features of Acute DIC?
1. Bleeding diathesis = tendency to bleed
2. Microangiopathic Hemolytic anemia
3. Multisystem involvement
4. Circulatory failure, shock

**Bleeding is the main problem = fulminant and rapidly occuring
What are the clinical features of Chronic DIC?
Thrombotic features predominate early
-happens slowly so the clotting factors may not be depleted all that much b/c you can make more
What is the treatment for DIC?
1. TREAT THE UNDERLYING DISORDER
2. Balanced use of anticoagulants and procoagulant based on clinical manifestations
What are the common causes of DIC?
1. Obstetric complications
-abruptio placentae
-Amniotic fluid

2. Infections
-Gram negative sepsis
-Meningococcemia

3. Neoplasms
-Acute Promyelocytic Leukemia
-Carcinomas of Lung, Stomach, Prostate, Pancreas

4. Massive Tissue Injury
-Trauma & Burns

5. Others
-Snakebite
-Liver disease
Increased PT, PTT, Fibrin-split products

Decreased Platelet count
DIC
Autosomal dominant disorder with a prolonged bleeding time and normal/prolonged PTT
von Willebrand disease
An 8-year-old boy presents to the emergency department with uncontrollable bleeding into his right knee joint. Upon taking a family history, you learn that 2 of the boy's maternal uncles suffer from a bleeding disorder. Lab tests reveal prolonged PTT, normal PT, and normal bleeding time.
Hemophilia
-X-linked
-bleeding into joints
-deficiency of factor 8 or 9
Compare the bleeding of Primary Hemostatis and Secondary Hemostasis disorders
Primary (Platelet Abnormalities) = Microhemorrhage = mucosal bleeding, petechiae, epistaxis

Secondary (Coagulation Factor defects) = Macrohemorrhage = hemarthroses, easy bruising