Fung: Coagulation II Flashcards Preview

Block 7 Week 4 > Fung: Coagulation II > Flashcards

Flashcards in Fung: Coagulation II Deck (53):
1

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

coagulation-type bleeding
platelet-type bleeding

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

coagulation type bleeding disorder

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

platelet type bleeding disorder

4

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

von Willebrand disease

5

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

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

6

Another name for von Willebrand factor

Ristocetin cofactor

7

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

factor 8

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

von Willebrand disease: Type 1

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

von Willebrand disease: Type 2

10

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

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

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)

Bernard Soulier syndrome

12

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

GPIb/V/IX

13

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

Bernard Soulier syndrome - giant platelets

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

Glanzmann thrombasthenia

15

What is deficient in Glanzmann thromasthenia?

GP IIb/IIIa (fibrinogen receptor)

**platelets don't have PLA1 antigen

16

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

ADP

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

17

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

second wave of aggregation

18

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

Aspirin
NSAIDs

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

19

Which has a reversible effect, aspririn or NSAIDs?

NSAIDs

20

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

disorders characterized by thrombocytopenia (low platelets)

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

immune thrombocytopenic purpura

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

22

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

thrombotic thrombocytopenic purpura

23

What are some of the symptoms expressed in TTP?

thrombocytopenia
microangiopathic hemolytic anemia
neuro abnormalities
renal abnormalities
fever

24

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

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

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)

Hemolytic uremic syndrome

26

Hemolytic uremic syndrome is most commonly associated with what??

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

**causes bloody diarrhea

27

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

heparin induced thrombocytopenia

28

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

IgG

29

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

thrombosis

30

3 symptoms of herparin induced thrombocytopenia?

thrombocytopenia
thrombosis
allergic reactions

31

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

factor 8; factor 8

32

How do patients with hemophilia A present?

with delayed bleeding
joint and muscle bleeding

33

What will the following values be like in hemophilia A?

PTT
platelet count
PT
TT

increased PTT
normal platelet count, PT and TT

34

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

factor 9; factor 9

35

How does hemophilia B present?

clinically identical to hemophilia A - delayed bleeding, joint and muscle bleeding

prolonged PTT, normal PT, TT

36

Liver disease can cause this...

decreased synthesis of most clotting factors, including fibrinogen

chronic DIC due to impaired clearance of D-dimer

37

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

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

38

List 4 things that can cause Vit K deficiency

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

39

Acquired syndrome characterized by the intravascular activation of coagulation

disseminated intravascular coagulation

40

Causes of disseminated intravascular coagulation?

endotoxin causing sepsis
trauma
burns
obstetrical complications
vascular malformations
animal venom

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)

tissue factor; tissue factor pathway inhibitor

42

What do fibrin formation and fibrinolysis cause in DIC?

microthrombi and consumption of clotting factors and platelets

43

Possible clinical manifestations in DIC

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

44

What does the differential diagnosis of thrombophilia depend on?

the type of thrombosis (arterial or venous)

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

Activated protein C resistance

46

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

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

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

anti-thrombin deficiency

48

What is the problem in anti-thrombin deficiency?

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

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

anti-phospholipid syndrome

50

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

Beta-2 glycoprotein
prothrombin

51

What is the difference between primary and secondary antiphospholipid syndrome?

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

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

prothrombin variant (G20210A)

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

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