Pathology - S2B2 - Blood 5

Front 1

What are the producers of von Willebrand Factor?

Back 1

1. Endothelial Cells
2. Megakaryocytes

**large multimers are cleaved by vWF cleaving protease (ADAMTS 13)

Front 2

What are the 2 functions of vWF?

Back 2

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

Front 3

What happens to Factor 8 if there is vWF deficiency?

Back 3

Factor 8 decreases b/c vWF stabilizes Factor 8 and prolongs its half-life

Front 4

Explain the 2 laboratory measurements of vWF

Back 4

1. Immunological assay = measures the total # of circulating molecules = quantity

2. Ristocetin Cofactor Activity = potentiates the binding of vWF to platelets = Functional assay (Qualitative)

Front 5

This is the most common hereditary bleeding disorder

Back 5

von Willebrand disease

Front 6

What are the 2 Quantitative defects in von Willebrand Disease?

Back 6

Type 1 = Autosomal dominant = mild deficiency

Type 3 = Autosomal recessive = Severe deficiency

Front 7

Describe Type 2A von Willebrand Disease

Back 7

Lack of larger (more active) multimers = lack of intermediate multimers = vWF is less active than it should be = Platelet Adhesion defect = Bleeding

Front 8

Describe Type 2B von Willebrand Disease

Back 8

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

Front 9

What are the lab findings in von Willebrand Disease?

Back 9

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

Front 10

What type are most cases of von Willebrand disease?

Back 10

Type 1 with mild or no bleeding

Front 11

What is the treatment of choice for Type 1 vWF disease?

Back 11

DDAVP = synthetic analog of Vasopressin --> increases the release of vWF from Endothelial cells

Front 12

What is the treatment of choice for Type 2 vWF disease?

Back 12

vWF replacement

**DDAVP would not work b/c you would just be releasing more non-functional vWF

Front 13

What is the deficiency in Hemophilia A?

Back 13

Factor 8 = Intrinsic Pathway

Front 14

What is the cause of Hemophilia A?

Back 14

X-linked recessive disease causing deficiency of Factor 8
-inversions, deletions, nonsense mutations, splicing errors

Front 15

What gender is more commonly affected by Hemophilia A and why?

Back 15

Males b/c it is an X-linked recessive disease

Front 16

What are 30% of cases of Hemophilia A due to?

Back 16

New mutations

**rarely cases are due to a functional defect, most are due to deficiency

Front 17

What are the lab findings associated with Hemophilia A?

Back 17

1. Prolonged PTT = Factor 8 = Intrinsic pathway

2. Normal Platelet count, BT/PFA, PT

3. Low Factor 8 levels

Front 18

List the percents of normal Factor 8 that produce:
1. Severe hemophilia A
2. Moderate
3. Mild

Back 18

1. < 1%
2. 2-5%
3. 6-50%

Front 19

What product can you not form in Hemophilia A?

Back 19

Fibrin clot = Secondary Hemostasis = Coagulation cascade

Front 20

This is the most common inherited bleeding disorder associated with SERIOUS BLEEDING

Back 20

Hemophilia A

Front 21

Describe the clinical findings associated with Hemophilia A

Back 21

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)

Front 22

What is the treatment for Hemophilia A?

Back 22

Recombinant Factor 8 replacement

Front 23

What is the complication with Recombinant Factor 8 replacement therapy in Hemophilia A? What is teh solution?

Back 23

15% produce Anti-Factor 8 Ab's

Give Recombinant Factor 7a = if you give excess 7a you can activate the common pathway

Front 24

What is the deficiency in Hemophilia B?

Back 24

Factor 9 = Intrinsic Pathway

**same as Hemophilia A except that Factor 9 is deficient and is much less common

Front 25

What are the lab findings for Hemophilia B?

Back 25

1. Prolonged PTT

2. Low factor 9 level

Front 26

What is the treatment for Hemophilia B?

Back 26

Recombinant Factor 9 Replacement therapy

Front 27

Why would Liver Disease be considered an acquired Coagulation Factor deficiency?

Back 27

Liver produces all Coagulation Factors except vWF

Front 28

What are the Lab findings in Coagulopathy of Liver Disease?

Back 28

1. Prolonged PT/PTT
2. Normal Platelet count; BT/PFA

Front 29

What factors are dependent on Vitamin K?

Back 29

2, 7, 9, 10, Protein C & S

Front 30

Vitamin K deficiency would casue deficiency of what factors?

Back 30

2
7
9
10
Protein C and S

Front 31

What would be the lab findings in Vitamin K deficiency?

Back 31

1. Prolonged PT/PTT

2. normal platelet count; BT/PFA

Front 32

What causes a deficient Vitamin K deficient state?

Back 32

Warfarin = inhibits Vitamin K Epoxide Reductase

Front 33

What Factor is most sensitive to Warfarin and there is the best indicator of Warfarin Anticoagulation?

Back 33

Factor 7 = Extrinsic Pathway = PT

**EX-PaTriot goes to WARfarin

Front 34

Describe the pathogenesis of Disseminated Intravascular Coagulation

Back 34

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

Front 35

Why are Schistocytes produced in DIC?

Back 35

Vascular occlusion by microthrombi causes Microangiopathic Hemolytic Anemia

Front 36

What are the lab findings in DIC?

Back 36

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

Front 37

What are the clinical features of Acute DIC?

Back 37

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

Front 38

What are the clinical features of Chronic DIC?

Back 38

Thrombotic features predominate early
-happens slowly so the clotting factors may not be depleted all that much b/c you can make more

Front 39

What is the treatment for DIC?

Back 39

1. TREAT THE UNDERLYING DISORDER
2. Balanced use of anticoagulants and procoagulant based on clinical manifestations

Front 40

What are the common causes of DIC?

Back 40

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

Front 41

Increased PT, PTT, Fibrin-split products

Decreased Platelet count

Back 41

DIC

Front 42

Autosomal dominant disorder with a prolonged bleeding time and normal/prolonged PTT

Back 42

von Willebrand disease

Front 43

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.

Back 43

Hemophilia
-X-linked
-bleeding into joints
-deficiency of factor 8 or 9

Front 44

Compare the bleeding of Primary Hemostatis and Secondary Hemostasis disorders

Back 44

Primary (Platelet Abnormalities) = Microhemorrhage = mucosal bleeding, petechiae, epistaxis

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