Fung: Coagulation II

Question 1

Clinically, most bleeding disorders can be divided into these two categories…

Answer 1

coagulation-type bleeding

platelet-type bleeding

Question 2

In this type of bleeding disorder, petechiae and mucosal bleeding are rare, but hemarthroses, deep hematomas and delayed bleeding are common; seen in males

Answer 2

coagulation type bleeding disorder

Question 3

In this type of bleeding disorder, petechiae and mucosal bleeding are common, but hemarthroses, deep hematomas and delayed bleeding are RARE; seen in females

Answer 3

platelet type bleeding disorder

Question 4

This is the most common inherited bleeding disorder; it is a defect in PLATELET ADHESION; combined platelet and coagulation defect; 4 main types

Answer 4

von Willebrand disease

Question 5

Where is von Willebrand factor synthesized? Where is it sotred? What does it do?

Answer 5

synthesized in endothelial cells and megakaryocytes; stored in Weibel-Palade bodies of endothelial cells and alpha granules of megakaryocytes; mediates platelet adhesion by binding GPIb

Question 6

Another name for von Willebrand factor

Answer 6

Ristocetin cofactor

Question 7

What does vWF complex with in the circulation to decrease its degradation?

Answer 7

factor 8

Question 8

Most common type and results in a mild bleeding disorder
QUANTITATIVE disorder showing reduced amounts of vWF
Laboratory evaluation will show
Normal PT
Prolonged PTT and BT
Decreased FVIII
Decreased vWF and activity

Answer 8

von Willebrand disease: Type 1

Question 9

Qualitative (functional) defect of vWF
4 subtypes
IIa
IIb
IIM – rare defect that prevents vWF binding to GPIb
IIN – rare defect with reduced vWF binding to FVIII

Answer 9

von Willebrand disease: Type 2

Question 10

What is the main difference between von Willebrand disease type IIa and type IIb?

Answer 10

IIa: absence of high molecular weight multimers, ristocetin cofactor (vWF) activity decreased;

IIb: decreased high molecular weight multimers, enhanced ristocetin cofactor, DO NOT give DDAVP

Question 11

Defect of platelet adhesion
Due to decreased platelet GPIb/V/IX
Patients clinically manifest with thrombocytopenia and giant platelets
Laboratory evaluation
PFT: aggregation on all agonists except ristocetin
Similar picture to vWD on PFT
Peripheral smear will show large platelets (unlike vWD)

Answer 11

Bernard Soulier syndrome

Question 12

In Bernard Soulier syndrome, platelet adhesion is defective due to a decrease in (blank)

Answer 12

GPIb/V/IX

Question 13

How can you differentiate von Willebrand disease from Bernard Soulier syndrome?

Answer 13

Bernard Soulier syndrome - giant platelets

Question 14

Autosomal recessive disorder due to deficient GP IIb/IIIa (fibrinogen receptor)
Platelets lack the PLA1 antigen
Laboratory evaluation
PFT: fail to aggregate with all agonists but ristocetin

Answer 14

Glanzmann thrombasthenia

Question 15

What is deficient in Glanzmann thromasthenia?

Answer 15

GP IIb/IIIa (fibrinogen receptor)

**platelets don’t have PLA1 antigen

Question 16

You can also have defects in granules of platelets. In alpha granule disease, aggregation is blunted with all agents except (blank)

Answer 16

ADP

• *one of the components of dense granules
• *associated with gray-platelet syndrome

Question 17

If you have dense granule disease, you will not get a (blank)

Answer 17

second wave of aggregation

Question 18

These two drugs can cause excessive bleeding by inhibiting COX-1 (the enzyme involved in thromboxane A2 production)

Answer 18

Aspirin
NSAIDs

**by blocking this enzyme, you will not get dense granule release and the secondary wave of aggregation

Question 19

Which has a reversible effect, aspririn or NSAIDs?

Answer 19

NSAIDs

Question 20

What are these?
Immune thrombocytopenic purpura (ITP)
Thrombotic thrombocytopenic purpura (TTP)
Hemolytic uremic syndrome (HUS)
Heparin induced thrombocytopenia (HIT)

Answer 20

disorders characterized by thrombocytopenia (low platelets)

Question 21

Diagnosis of exclusion: healthy patient with isolated thrombocytopenia with no other obvious cause
Antigenic target of the antibody varies
GP IIb
GP IIIa
GP Ib
GP V

Answer 21

immune thrombocytopenic purpura

**when there is no other cause for the thrombocytopenia, consider this

Question 22

Syndrome resulting from widespread formation of microvascular platelet thrombi affecting
Central nervous system
Kidneys
Gastrointestinal tract
Other organs

Answer 22

thrombotic thrombocytopenic purpura

Question 23

What are some of the symptoms expressed in TTP?

Answer 23

thrombocytopenia
microangiopathic hemolytic anemia
neuro abnormalities
renal abnormalities
fever

Question 24

In thrombotic thrombocytopenic purpura, there is an acute deficiency in vWF-cleaving metalloprotease. What does this lead to?

Answer 24

an accumulation of ultra-large vWF multimers which bind platelets and lead to thrombi in the microvasculature and thrombocytopenia

Question 25

Thrombotic microangiopathy characterized by Thrombocytopenia Acute renal failure Microangiopathic hemolytic anemia Most commonly associated with bloody-diarrhea caused by shiga-toxin producing bacteria (E. coli O157:H7 or S. dysenteriae)

Answer 25

Hemolytic uremic syndrome

Question 26

Hemolytic uremic syndrome is most commonly associated with what??

Answer 26

shiga toxin producing bacteria (like E. coli O157:H7 or S. dysenteriae) **causes bloody diarrhea

Question 27

Occurs in 1-3% of patients treated with unfractionated heparin for greater than 5 days

Answer 27

heparin induced thrombocytopenia

Question 28

Heparin induced thrombocytopenia is an immune mediated disorder caused by (blank) antibodies against the complex of heparin and PF4

Answer 28

IgG

Question 29

Which is more common in heparin induced thrombocytopenia, bleeding or thrombosis?

Answer 29

thrombosis

Question 30

3 symptoms of herparin induced thrombocytopenia?

Answer 30

thrombocytopenia thrombosis allergic reactions

Question 31

Hemophilia A is a congenital X-linked recessive deficiency in (blank), which results in absent circulating (blank) and lifelong bleeding

Answer 31

factor 8; factor 8

Question 32

How do patients with hemophilia A present?

Answer 32

with delayed bleeding | joint and muscle bleeding

Question 33

What will the following values be like in hemophilia A? PTT platelet count PT TT

Answer 33

increased PTT | normal platelet count, PT and TT

Question 34

Hemophilia B is due to a congenital X-linked recessive deficiency in (blank), which results in decreased or absent (blank) and lifelong bleeding

Answer 34

factor 9; factor 9

Question 35

How does hemophilia B present?

Answer 35

clinically identical to hemophilia A - delayed bleeding, joint and muscle bleeding prolonged PTT, normal PT, TT

Question 36

Liver disease can cause this...

Answer 36

decreased synthesis of most clotting factors, including fibrinogen chronic DIC due to impaired clearance of D-dimer

Question 37

Vit K deficiency leads to impaired production of Vit K dependent clotting factors. What are they?

Answer 37

``` factor II Factor 7 factor 9 factor 10 protein C protein S ```

Question 38

List 4 things that can cause Vit K deficiency

Answer 38

hemorrhagic disease of the newborn **newborns get a shot of Vit K to avoid this antibiotics **knocks out gut flora, so decreased Vit K absorption malabsorption/malnutrition warfarin therapy

Question 39

Acquired syndrome characterized by the intravascular activation of coagulation

Answer 39

disseminated intravascular coagulation

Question 40

Causes of disseminated intravascular coagulation?

Answer 40

``` endotoxin causing sepsis trauma burns obstetrical complications vascular malformations animal venom ```

Question 41

In DIC, the patient will have prolonged exposure to (blank) resulting in generalized activation of the coag system and thrombin generation. In addition, there will be no activation of (blank)

Answer 41

tissue factor; tissue factor pathway inhibitor

Question 42

What do fibrin formation and fibrinolysis cause in DIC?

Answer 42

microthrombi and consumption of clotting factors and platelets

Question 43

Possible clinical manifestations in DIC

Answer 43

``` hemorrhage renal/hepatic/respiratory dysfunction shock CNS dysfunction petechiae purpura skin necrosis ```

Question 44

What does the differential diagnosis of thrombophilia depend on?

Answer 44

the type of thrombosis (arterial or venous)

Question 45

Inherited autosomal dominant condition responsible for 50% of the cases of hereditary thrombophilia Due to a point mutation in the FV gene that makes FV Leiden resistant to proteolytic cleavage by APC Heterozygotes have 5-10 increased risk of thrombosis

Answer 45

Activated protein C resistance

Question 46

What does activated protein C (APC) do? In activated protein C resistance (APCR), what is the problem?

Answer 46

Activated protein C usu degrades factor 5a and 8a; if these cannot be degraded, may lead to longer duration of thrombin generation and increased risk of thrombosis

Question 47

Autosomal dominant disorder characterized by recurrent venous thrombosis No inactivation of Factors II, IXa, Xa, XIa, XIIa Heterozygotes have 5-10 increased risk of thrombosis Homozygosity is considered incompatible with life

Answer 47

anti-thrombin deficiency

Question 48

What is the problem in anti-thrombin deficiency?

Answer 48

no inactivation of factors II, 9a, 10a, 11a, and 12a which leads to recurrent venous thrombosis

Question 49

``` An autoimmune thrombophilic condition in which patients have circulating antibodies against plasma proteins that bind to phospholipids Patients have Recurrent arterial and venous thrombosis Pregnancy loss Immune cytopenias ```

Answer 49

anti-phospholipid syndrome

Question 50

What are some things that you might form antibodies to in antiphospholipid syndrome?

Answer 50

Beta-2 glycoprotein | prothrombin

Question 51

What is the difference between primary and secondary antiphospholipid syndrome?

Answer 51

primary APL: healthy individuals | secondary APL: associated w disease (lupus, HIV, cancers, drugs)

Question 52

Autosomal dominant condition due to a point mutation in the prothrombin gene Mutation enhances prothrombin gene transcription leading to elevated levels of prothrombin Second most common cause of inherited thrombophilia

Answer 52

prothrombin variant (G20210A)

Question 53

Inherited autosomal dominant form with heterozygotes with 5-7 fold increased risk of thrombosis Acquired form may result from Coumadin therapy Liver disease Pregnancy Deficiency can either be due to qualitative or quantitative defects

Answer 53

Protein C/S deficiency **Protein C inactivates factor 5 and 8, so you lose your checks and balances in the coag cascade and this leads to excessive thrombosis