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Flashcards in Other Disorders of Hemostasis Deck (59):
1

A disorder of platelet destruction that is secondary to heparin therapy…

Heparin-induced thrombocytopenia

2

With heparin-induced thrombocytopenia, how can the development of thrombosis occur?

Fragments of destroyed platelets may activate the remaining platelets causing a thrombosis

3

What does heparin form a complex with in heparin-induced thrombocytopenia and what does this cause the formation of?

Forms a complex with PF4 causing the formation of IgG antibodies against the platelets

4

A pathological activation of the coagulation cascade with widespread microthrombi that results in ischemia and infarction…

Disseminated intravascular coagulation (DIC)

5

What is the mechanism of excessive bleeding from IV sites and mucosal surfaces observed in disseminated intravascular coagulation?

With DIC there is a rapid consumption of platelets and coagulation factors which lead to the excessive bleeding

6

Disseminated intravascular coagulation is almost always secondary to another disease. What are the 5 most common diseases that can cause DIC?

1) Obstetric complications
2) Sepsis
3) Adenocarcinoma
4) Acute promyelocytic leukemia
5) Rattlesnake bite

7

What is the mechanism of disseminated intravascular coagulation formation an obstetrical patient?

Tissue thromboplastin within the amniotic fluid activates the coagulation cascade

8

Sepsis can cause disseminated intravascular coagulation. What is the mechanism of action?

Endotoxins from bacterial wall (E. coli or N meningitides) and cytokines induce endothelial cells to make tissue factor.

9

What activates the coagulation cascade when disseminated intravascular coagulation occurs secondary to adenocarcinoma?

Mucin

10

Patients with acute promyeloctic leukemia can develop disseminated intravascular coagulation. What causes the activation of the coagulation cascade?

Primary granules

11

A bite can cause disseminated intravascular coagulation. What animal can cause this and what is produced by the animal to cause DIC?

Rattlesnake bite—venom causes activation of coagulation cascade→ DIC

12

What are the laboratory findings with disseminated intravascular coagulation with respect to PT, PTT, Platelet count, and Fibrinogen?

PT: elevated
PTT: elevated
Platelet count: decreased
Fibrinogen: decreased

13

What type of anemia is seen with disseminated intravascular coagulation?

Microangiopathic hemolytic anemia

14

What is the best screening test for disseminated intravascular coagulation?

Elevated D-dimer

Derived from splitting of cross-linking fibrin

15

What is the treatment for disseminated intravascular coagulation?

Treatment of underlying cause and blood transfusion and cryoprecipitate.

16

What is the purpose of fibrinolysis?

Removal of thrombus after damaged vessel has healed.

17

What are the 3 steps of fibrinolysis?

1) tPA conversion of plasminogen to plasmin
2) Plasmin cleaves fibrin and serum fibrinogen—destroying the coagulation factors and blocks platelet aggregation
3) A2-antiplasmin inactivates plasmin

18

What is responsible for the conversion of plasminogen to plasmin during fibrinolysis?

tPA-(tissue plasminogen activator)

19

After fibrinolysis has occured, what inactivates the plasmin to stop its function?

A2-antiplasmin

20

Disorders of fibrinolysis usually involve over activity of what substance?

Plasmin

21

Over activity of plasmin seen in disorders of fibrinolysis causes what to occur?

Excessive cleavage of serum fibrinogen

22

What are the 2 most common causes of disorders to fibrinolysis?

Radical prostatectomy
Cirrhosis of the liver

23

What is release during a radical prostatectomy that causes a disorder of fibrinolysis?

Urokinase

24

When urokinase is released during a radical prostatectomy, what occurs to allow for the disorder of fibrinolysis?

Urokinase activates plasmin

25

Why does cirrhosis of the liver cause disorders in fibrinolysis?

There is a reduction in the production of a2-antiplasmin, which allows plasmin to remain activated.

26

What are the typical laboratory findings seen with disorders of fibrinolysis with respect to PT/PTT, bleeding time, Platelet count, and fibrinogen levels?

PT/PTT: elevated
Bleeding time: elevated
Platelet count: normal
Fibrinogen: decreased (without D-dimers)

27

How can a disorder of fibrinolysis be differentiated from disseminated intravascular coagulation?

DIC will have D-dimers with the splitting of fibrinogen and DIC will also have a decreased platelet count. Disorder of fibrinolysis will have normal platelet count

A disorder of fibrinolysis will have ABSENCE of D-dimer because fibrin thrombi are absent

28

What is the treatment for a disorder of fibrinolysis?

Aminocaproic acid—this blocks the activation of plasminogen

29

Where is the most common location for thrombosis formation?

Deep veins (DVT) of the leg below the knee

30

What are the two characteristics of a thrombosis and why are these important findings on autopsy?

Lines of Zahn and attachment to vessel wall

If found on autopsy—indicates that thrombosis occur prior to death

31

What are the 3 major risk factors contributing to thrombosis formation also known as Virchow triad?

1) Disruption in blood flow
2) Endothelial cell damage
3) Hypercoagulable state

32

What are the 3 common disruptions in normal blood flow that can lead to the formation of thrombosis?

1) immobilization—increased risk of DVT
2) Cardiac wall dysfunction—(a-fib, MI)
3) Aneurysm

33

What are the 5 ways in which endothelial cells prevent the formation of thrombosis?

1) Blockage of exposure to subendothelial collagen and underlying tissue factor
2) Production of PGI2 and NO—vasodilatation and inhibition of platelet aggregation
3) Secretion of heparin-like molecules—ATIII augmentation causing inactivation of thrombin and coagulation factors
4) Secretion of tPA
5) Scretion of thrombomodulin

34

The production of PGI2 and NO to prevent thrombosis formation works through what mechanism(s)?

Cause vasodilation and inhibition of platelet aggregation

35

How does the secretion of heparin-like molecules prevent the formation of thrombosis?

Causes augmentation of antithrombin III (ATIII), which in turn inactivates throbin and coagulation factors

36

The secretion of tPA stops the formation of thrombosis through what mechanism?

Converts plasminogen to plasmin—this does 3 things
1) cleaves fibrin and serum fibrinogen
2) destroys coagulation factors
3) blocks platelet aggregation

37

The secretion of thrombomodulin prevents the formation of thrombosis through activation of what?

Causes redirection of the thrombin to activate protein C—this in turn inactivates factor V and VIII

38

What are the 3 most common causes of endothelial cell damage?

Atherosclerosis
Vasculitis
High levels of homocysteine

39

What 2 deficiencies cause a mild elevation of homocysteine levels, which increase the risk of thrombosis formation?

Vitamin B12 deficiency
Folate deficiency

40

What is the mechanism for increased homocysteine levels with a vitamin B12 or folate deficiency?

Lack of Vitamin B12 or folate leads to the decreased conversion of homocysteine to methionine due to the inability to transfer a methyl group. This leads to a build up of homocysteine

41

A deficiency in cystathionine beta synthase (CBS) causes a high level of what substance?

Homocysteine

42

What is the enzymatic function of cystathionine beta synthase (CBS)?

Conversion of homocysteine to cystathionine

43

What are the 4 characteristic findings seen in patients who present with a cystathionine beta synthase (CBS) deficiency?

1) Vessel Thrombosis
2) Mental retardation
3) Lens dislocation
4) Long slender fingers

44

What is the classic presentation of a patient who presents with a hypercoagulable state?

Reccurent DVTs or DVT at a young age

45

What are the most common sites for DVTs to occur?

Deep veins of the leg
Hepatic and cerebral veins

46

What deficiency is typically found with patients who have a hypercoagulable state?

Protein C and S deficiency

47

What does a protein C and S deficiency cause within the coagulation cascade?

Deficiency decreases the negative feedback on the coagulation cascade

48

What is the normal function of protein C and S within the coagulation cascade?

Inactivate factors V and VIII

49

Patients who present with a protein C and S deficiency are at an increased risk of developing what type of necrosis?

Warfarin skin necrosis

50

A disease involving a mutated form of factor V that results in the factor V without a cleavage site for deactivation by protein C and S…

Factor V Leiden

51

What is the most common inherited cause of a hypercoagulable state?

Factor V Leiden

52

A disease involving an inherited point mutation in prothrombin resulting in an increased gene expression of prothrombin…

Prothrombin 20210A

53

How does prothrombin 20210A promote the production of thrombus?

Increased prothrombin→ increased thrombin→ thrombus formation

54

This deficiency decreases the protective effect of heparin-like molecules produced by the endothelium, which increases the risk of thrombus formation…

ATIII deficiency

55

What do heparin-like molecules normally activate and what role does this play in the coagulation pathway?

Activates ATIII, which inactivates thrombin and coagulation factors

56

What laboratory measurement is used to monitor heparin therapy?

PTT

57

A patient presents with ATIII deficiency and is given heparin. What laboratory value will be different when comparing it to a patient WITHOUT ATIII deficiency who was given heparin?

The PTT level does not rise with standard heparin dosing in the patient with the ATIII deficiency

58

What is given to overcome an ATIII deficiency and maintain an anticoagulated state?

A high dose of heparin is given to activate the limited number of ATIII and then Coumadin is given to maintain an anticoagulated state

59

What is the mechanism by which oral contraceptives increase the risk of developing a hypercoagulable state?

Estrogen within the oral contraceptive will increase the production of the coagulation factors—this increases the risk of thrombosis