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Flashcards in Coagulation Deck (65):
1

Primary hemostasis: name the membrane receptor, Adhesive protein, and appropriate surface

Membrane receptor: Glycoprotein 1b

Adhesive protein: Von Willebrand factor

Appropriate surface: Subendothelial matrix (collagen)

2

name the events that occur during platelet activation:

* platelets are activated by binding to vWF

Secretion – alpha-granules and dense bodies (2nd messengers)

* Activation of GP IIb/IIIa receptor

* Shape change – from rounded discs to flat plates

3

what protein is responsible for holding platelets together during aggregation?

fibrinogen

4

what steps occur during secondary hemostasis?

Secondary hemostasis = fibrin clot formation

Formation of thrombin

Formation of fibrin clot
- with crosslinking of fibrin monomers by Factor XIIIa

5

what molecules will inhibit secondary hemostasis?

Serine protease inhibitors (antithrombin)

Protein C pathway (controls Va and VIIIa)

Fibrinolytic system (removes excess clot- TPA)

6

what are the components of Anti-thrombin?

Serine Protease

+

SERPIN

7

Serine protease + SERPIN forms what?

Enzyme-Inhibitor Complex

(antithrombin

8

what molecules does serine protease (antithrombin) inhibit?

Thrombin

factors IXa, Xa, XIa, and XIIa

9

Activated Protein C (APC) plus Protein S serve to inactivate cofactors __________

Va and VIIIa

(the major Cofactors in coagulation cascade)

10

Protein C or Protein S deficiencies result in _________________

hypercoaguable states

11

what are the effects of a Factor V Leiden mutation?

promotes coagulation

(resistance to enzymatic inactivation by the Protein C/S complex)

12

In the presence of fibrin, _________________ can bind to plasminogen and convert it to an active enzyme, plasmin

tissue plasminogen activator (TPA)

13

Plasmin breaks down previously cross-linked fibrin monomers into what?

fibrin degradation products (FDP)

14

Uncontrolled activation of plasmin can result in bleeding complications as ____________ and _____________

fibrinolysis and fibrin(ogen)olysis

15

___________ inhibits serine proteases

antithrombin

16

protein C inhibits ________

cofactors Va and VIIIa

17

what are the screening tests of hemostasis?

Prothrombin Time (PT)
Partial Thromboplastin Time (PTT)
Platelet count
Bleeding time (BT)/PFA-100

18

The most important part of defining the cause of a bleeding disorder is _______________

a careful clinical history

19

Prothrombin Time (PT) screens for activity of proteins in the __________ pathway

extrinsic

(factors V, VII, II, X and fibrinogen)

20

Partial thromboplastin time (PTT) screens for activity within the _________ pathway

intrinsic

(factors XII, XI, IX, VIII... X, V, II and fibrinogen)

21

what is the normal range for platelet counts?

normal range is generally 150,000 to 400,000/µL

22

what is thrombocytopenia? thrombocytosis? thrombocythemia?

- thrombocytopenia refers to a decrease in platelet number

- thrombocytosis and thrombocythemia denote an increase in platelet number

23

what do the results of a positive mixing test show? what about a negative test?

- If the mixing study corrects the clotting time, a deficiency of some factor(s) is felt to be present

- If the mixing study does not correct the clotting time, an inhibitor is felt to be present, either factor-specific or lupus anticoagulant type

24

how are bleeding disorders classified?

Congenital vs. Acquired
Mild vs. Severe
Primary vs. Secondary Hemostasis
Regulatory Disorder

25

what are the CLINICAL manifestations of Disorders of Primary Hemostasis ?

Mucocutaneous bleeding (vWF disease)
Excessive bleeding with trauma (vWF-d, Hemophilia A &B)

26

what are the lab findings of Disorders of Primary Hemostasis ?

- Prolonged BT/PFA-100
- Thrombocytopenia

27

what are the clinical manifestations of Disorders of secondary Hemostasis ?

- Soft tissue bleeding

- Excessive bleeding with trauma

28

what are the lab findings of Disorders of secondary Hemostasis ?

Prolonged PT and PTT

Prolonged TT (thrombin time)

29

what are the clinical manifestations of regulatory disorders of Hemostasis ?

Soft tissue bleeding

Excessive bleeding with trauma

30

what are the lab findings of regulatory disorders of Hemostasis ?

Normal PT and PTT
Normal bleeding time
Normal platelet count

31

list the characteristics of von Willebrand disease:

Autosomal dominant disorder (usually)

Due to abnormalities of vWF

Abnormality may be quantitative, qualitative or both

Mucocutaneous bleeding is the dominant clinical manifestation

32

what is the Factor VIII Complex?

vWF + factor VIII procoagulant

33

what is the most commonly inherited bleeding disorder?

von Willebrand disease

- effects 1% of population

34

what are the 3 classes/types of von Willebrand disease?

Type 1: Quantitative deficiency (partial)
Type 2: Qualitative deficiency
Type 3: Quantitative deficiency (total)

35

clinical manifestations of von Willebrand disease:

*mucosal bleeding (NOT SEEN in hemophilia A)
Epistaxis (nosebleeds)
Ecchymoses (>1cm bruises)
Bleeding with trauma or surgery
Symptoms improve after adolescence

36

in a patient with vWD, what lab tests would be normal? which would be elevated/prolonged? which would decrease?

PT & platelet count = normal

BT/PFA-100: Prolonged
*PTT: prolonged
*VIII: Decreased
vWF:ag: Decreased
vWF:Rcof: Decreased

37

treatments for vWD include what?

Desmopressin
Antifibrinolytic agents
Factor VIII concentrates
Cryoprecipitate

38

list the general characteristics of Hemophilia A:

Sex-linked recessive disorder

Deficiency of factor VIII

Recurrent soft tissue bleeding

Symptoms usually start in early childhood

39

clinical characteristics of Hemophilia A:

Hemarthrosis
Soft tissue bleeding
Excessive bleeding with trauma
Intramuscular hematomas
Intracerebral hemorrhage
Bleeding into other tissues

40

which lab tests are ABNORMAL for Hemophilia A? (include wether they are prolonged or decreased)

PTT: Prolonged

Factor VIII: Decreased


(PT time is normal- no effect on extrinsic clotting)

41

what is "Severe" hemophilia A? what is its characteristics?

<1% factor VIII

Recurrent spontaneous soft tissue and joint space bleeding

42

what are the characteristics of moderate and mild Hemophilia A?

Moderate:
1 - 5% factor VIII
Bleeding with minor trauma

Minor:
>5% factor VIII
Bleeding with major trauma

43

what treatments are used for Hemophilia A?

Factor VIII Concentrates

Fibrinolytic inhibitors

44

list the disease related complications of Hemophilia A:

Arthritis and joint destruction
Pseudotumors
Intracranial bleeding
Retroperitoneal bleeding

45

list the treatment related complications of Hemophilia A:

Antibodies to factor VIII
Infectious diseases

46

list the characteristics of Hemophilia B:

- Sex-linked, recessive disorder
- Deficiency of factor IX (INTRINSIC pathway)
- Clinical and laboratory presentation similar to deficiency of factor VIII

Mild, moderate, severe deficiencies are seen
Mild cases may be difficult to recognize clinically

47

list the disease related complications of Hemophilia B:

SAME AS HEMOPHILIA A

Arthritis and joint destruction
Pseudotumors
Intracranial bleeding
Retroperitoneal bleeding

48

list the treatment related complications of Hemophilia B:

Antibodies to factor IX
Infectious diseases

49

what are the mechanisms for thrombocytopenia?

Decreased platelet production
Increased destruction
Sequestration
Congenital versus acquired

50

list the clinical characteristics of Acute/childhood ITP

(ITP = immune thrombocytopenia purpura)

Viral prodrome (early symptom) common
Sudden onset
Severe thrombocytopenia
Frequently undergoes spontaneous remission
M:F close to 1:1

51

list the clinical characteristics of Adult/chronic TTP

(TTP = thrombotic thrombocytopenia purpura)

No antecedent infection
Gradual onset
Moderate thrombocytopenia
Infrequent spontaneous remission
More common in females

52

what are the clinical characteristics of all ITP's?

Petechiae
Ecchymoses (bruising)
Bleeding with trauma or surgery

53

what is the pathophysiology for ITP?

- Autoantibodies directed at the platelet membrane antigens

- GPIb/IX and IIb/IIIa common targets

- Increased IgG bound to the platelet surface promotes increased sequestration/destruction by the reticuloendothelial system

54

what changes in the blood and bone marrow can be seen during ITP?

Megakaryocytes normal to increased

No microangiopathic changes on blood smear review

55

Therapy for ITP includes:

Corticosteroids
Intravenous immunoglobulin
Immunosuppression
Splenectomy

56

what is Thrombotic Thrombocytopenic Purpura (TTP)?

- Acute disorder characterized by intravascular platelet activation with formation of platelet-rich microthrombi throughout the circulation

- Left untreated, TTP is associated with high mortality.

57

TTP is Now known to be caused by a deficiency of ____________, a metalloproteinase

ADAMTS 13

58

what does the ADAMTS 13 metalloproteinase do?

degrades very-high-molecular-weight vWF

59

what lab method is used to detect TTP?

HUS-TTP spectrum

60

what is Disseminated Intravascular Coagulation (DIC)?

Unregulated, widespread intravascular activation of the hemostatic system

Systemic formation of thrombin and plasmin with consumption of clotting factors and bleeding

61

the result of DIC is the formation of what 2 conditions?

- microvascular thrombosis

- hemorrhaging

62

what can cause DIC?

Infections (gram negative sepsis)

Tissue injury (trauma, burn, surgery)

Obstetrical complications

Certain malignancies

63

list all the clinical signs of DIC:

Bleeding from multiple sites
Thromboembolic problems
Hypotension and shock
Respiratory dysfunction
Hepatic dysfunction
Renal dysfunction
CNS dysfunction

64

During therapy for DIC, what blood products can be transfused?

FFP: coagulation & regulatory proteins

Cryo: fibrinogen, VIII, vWF

Platelets: platelets

65

heparin works in the same way as what enzyme/Factor in the coagulation cascade?

antithrombin