Coagulation Disorders Flashcards

1
Q

List 3 phases of primary hemostasis (platelet response).

A

Adhesion
Activation
Aggregation

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2
Q

Hemostasis refers to the ability to maintain blood in a ______ state and prevent loss from sites of _______ damage.

A

fluid

vascular

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3
Q

Name the three major components of the hemostatic system.

A

vascular wall
platelets
coagulation proteins

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4
Q

What occurs during adhesion?

A
  • adhesion of platelets to the damaged endothelial site
  • involves activation of a surface membrane receptor (glycoprotein Ib/IX), an adhesive protein (von Willebrand factor), and an appropriate surface (sub endothelial collagen)
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5
Q

What mediates the adherence of platelets to the subendothelial collagen?

A

vWF

glycoprotein Ib/IX binds to vWF

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6
Q

During activation, additional _______ are recruited into the local site.

A

platelets

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7
Q

As platelets are activated by binding to vWF, there is release of secondary messengers within the platelet that lead to a shape change from ________ to ________

A
discoid
flatter (elongated) 
Note: this shape change increases surface area
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8
Q

During aggregation, platelet-platelet binding is mediated through…

A

fibrinogen and the glycoprotein IIb/IIIa receptor

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9
Q

Fibrin clot formation is referred to as _________ hemostasis.

A

secondary

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10
Q

Thrombin converts ______ to ______ which adds stability to the clot after ______ monomers are covalently cross linked by Factor ___.

A

fibrin
fibrinogen
fibrin
XIII

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11
Q

The _________ pathway refers to the sequence of activation of Factor XII by Kallikrein.

A

intrinsic

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12
Q

After activation of Factor XII during the intrinsic pathway, Factor XIIa activates Factor __.

A

XI

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13
Q

Factor ___ activates IX.

A

XIa

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14
Q

The ________ pathway refers to the sequence of activation of Factor VII by tissue factor.

A

extrinsic

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15
Q

The _______ pathway involves activation of X to __, followed by conversion of prothrombin (II) to _______, followed by conversion of fibrinogen (I) to ________ monomers.

A

common
Xa
thrombin
fibrin

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16
Q

What is formed when fibrin monomers generated by thrombin polymerize to form a long strand?

A

fibrin clot

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17
Q

What makes the fibrin monomers more stable?

A

covalent cross-linking by Factor XIII

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18
Q

These inhibit the activity of thrombin and other serine proteases (factors IXa, Xa, XIa, XIIa) of the coagulation cascade by forming inactive ________-________ complex.

A

antithrombins

enzyme-inhibitor

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19
Q

This is one of the best known antithrombins that, in the presence of heparin, becomes activated to that it can form a complex with thrombin (preventing thrombin from generating fibrin monomers).

A

antithrombin III

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20
Q

What system regulates the major cofactors of the coagulation cascade, factor Va and VIIIa.

A

protein C system

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21
Q

What is the major effector enzyme in the protein C system?

A

Activated protein C (APC)

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22
Q

What is a major cofactor in the protein C system?

A

protein S

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23
Q

Protein C or protein S deficiencies lead to __________ states.

A

hypercoaguable

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24
Q

Factor V Leiden mutation promotes _________.

A

coagulation

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25
Q

Tissue plasminogen activator (TPA) can bind to __________ and convert it to an active enzyme, _______.

A

plasminogen

plasmin

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26
Q

Plasmin breaks down previously cross-linked fibrin monomers into _____ _________ ______ or (____).

A

fibrin degradation products (FDP)

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27
Q

Uncontrolled activation of plasmin can result in ________ complications due to fibrinolysis.

A

bleeding

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28
Q

Shifts in the balance that favor the procoagulant side result in _________, whereas shifts that favor the regulatory side can result in _________ disorders.

A

thrombosis

bleeding

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29
Q

The most important part of defining the cause of a bleeding disorder is a careful _______ _______.

A

clinical history

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30
Q

This lab test is a measurement of the time needed for plasma to form a clot in the presence of added tissue thromboplastin (to initiate extrinsic coagulation cascade) and calcium ions.

A

Prothrombin time (PT)

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31
Q

Prolonged PT results from _________ or ________ in Factors VII, X, V, II, and/or fibrinogen

A

decreases

abnormalities

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32
Q

This lab test is routinely used to measure degree of anticoagulation in patients receiving coumadin.

A

PT

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33
Q

This is a ratio of the patient PT time/control PT time. Also used to monitor coumadin patients.

A

INR

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34
Q

This lab test is a measurement of the time needed for plasma to form a clot in the presence of added ground glass or kaolin (to activate contact-dependent Factor XII), cephalin (phospholipid), and calcium ions.

A

partial thromboplastin time (PTT)

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35
Q

This lab test primarily accesses the intrinsic coagulation cascade.

A

PTT

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36
Q

Prolonged PTT can result from decreases or abnormalities of which 7 factors and fibrinogen?

A
II
V
VIII
IX
X
XI
XII
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37
Q

This lab test is routinely used to measure degree of anticoagulation in patients receiving heparin therapy.

A

PTT

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38
Q

This lab test is a measurement of platelet number in anticoagulated blood quantitated by an automated instrument.

A

platelet count

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39
Q

Normal range of platelet count is generally ________ to ________ /uL.

A

150,000

400,000

40
Q

This term refers to a decrease in platelet number.

A

thrombocytopenia

41
Q

These two terms denote an increase in platelet number.

A

thrombocytosis

thrombocythemia

42
Q

This lab test is a measurement of platelet function as determined by the time taken for a standardized skin incision to stop bleeding.

A

bleeding time

43
Q

This lab test is no longer used and has been replaced by the ___-___.

A

bleeding time

PFA-100

44
Q

When either PT or PTT is prolonged, a ________ study with 1:1 ratio of normal plasma:patient plasma can be performed.

A

mixing

45
Q

If the mixing study corrects the clotting time, a deficiency of some _______ is felt to be present.

A

factors

46
Q

If the mixing study does not correct the clotting time, an _________ is felt to be present.

A

inhibitor

47
Q

More specialized test may be necessary to precisely define a coagulation defect - these include:

A
  • assays for specific coagulation factors
  • measurement of fibrinogen quantity and function
  • platelet aggregation tests
48
Q

What are the 3 classifications of bleeding disorders?

A

Disorders of:
primary hemostasis
secondary hemostasis
regulatory system

49
Q

Clinical manifestations of these types of disorders include mucotaneous bleeding/bleeding associated with trauma.
Labs will show prolonged bleeding time and thrombocytopenia.

A

Disorders of primary hemostasis

50
Q

Clinical manifestations of these types of disorders include soft tissue bleeding/bleeding associated with trauma.
Labs will show prolonged PT/PTT/thrombin time.

A

Disorders of secondary hemostasis

51
Q

Clinical manifestations of these types of disorders include soft tissue bleeding/bleeding associated with trauma.
Labs will often be normal in screening tests.

A

Disorders of the regulatory system

52
Q

Name the 3 congenital bleeding disorders discussed in class.

A

von Willebrand Disease
Hemophilia A
Hemophilia B

53
Q

Name the 3 platelet disorders discussed in class.

A

thrombocytopenia
Immune Thrombocytopenic Purpura (ITP)
Thrombotic Thrombocytopenic Purpura (TTP)

54
Q

This disorder results from uncontrolled activation of the hemostatic system.
Both systemic thrombin formation and systemic plasmin formation occur.

A

Disseminated Intravascular Coagulation (DIC)

55
Q

What are the two components of the Factor VIII complex?

A

vWF

Factor VIII procoagulant

56
Q

What are 2 functions of vWF?

A
  • carrier molecule for Factor VIII

- the “glue” between damaged endothelium and platelets (in primary hemostasis)

57
Q

When is Factor VIII procoagulant released from vWF?

A

when a clot is formed (Factor VIII then participates in generating Factor X)

58
Q

T/F

The half life of vWF when not bound to Factor VIII is very long.

A

False

very short

59
Q

Where is Factor VIII believed to be synthesized?

A

liver

60
Q

Where is vWF present?

A

in platelets and endothelial cells

61
Q

This disease is associated with decreased amounts of a normal protein (quant. abnormality) or production of a protein with abnormal function (qual. abnormality), or both.

A

von Willebrand Disease

62
Q

This is the most common inherited bleeding disorder affected approximately 1% of the U.S. population.

A

von Willebrand Disease

63
Q

What is the predominant clinical manifestation of von Willebrand Disease?

A

mucocutaneous bleeding

nosebleeds, bruising, mucosal bleeding, excessive bleeding with trauma/surgery, or excessive menstrual flow

64
Q

When do symptoms of von Willebrand Disease often improve?

A

after adolescence

65
Q

The most common form of vWD results in production of _________ amounts of vWF which also results in ________ amounts of Factor VIII.

A

decreased

decreased

66
Q

Labs of vWD patients show prolonged _______ ____ and prolonged ___. Platelet aggregation studies may be abnormal in about ___ of patients.

A

bleeding time
PTT
1/3

67
Q

What 2 drugs can be given as treatment for mild vWD?

A
  • desmopressin

- anti-fibrinolytic agents

68
Q

What does desmopressin do in the body?

A

releases vWF from endothelial cells

69
Q

What is given in more severe cases of vWD?

A
  • Factor VIII concentrates containing vWF

- cryoprecipitate

70
Q

This disease is due to decreased production of Factor VIII and is the most common hereditary cause for serious bleeding.

A

Hemophilia A

71
Q

The clinical hallmark of Hemophilia A is recurrent…

Symptoms usually start ______ in life.

A

soft tissue bleeding

early

72
Q

Other clinical manifestations of Hemophilia A are:

A
  • hemarthrosis
  • bleeding with trauma
  • intramuscular hematomas
  • intracranial hemorrhage
  • excessive bleeding in general
73
Q

T/F

There is a high rate for de novo mutations resulting in Hemophilia A.

A

True

about 30%

74
Q

Labs of patients with Hemophilia A will show _______ bleeding time, ________ PTT, ________ VIII, and normal ___ and ___.

A
normal
prolonged
decreased
vWF
IX
75
Q

Severe Hemophilia A is characterized by a Factor VIII level of…

A

<1%

76
Q

Moderate forms of Hemophilia A have ____% VIII and mild forms have ___%

A

1-5

>5

77
Q

The severity of bleeding with Hemophilia A is directly proportional to the amount of ____ present.

A

VIII

78
Q

Treatment of Hemophilia A involves replacement of ________ in the form of concentrates.

A

Factor VIII

79
Q

These two things may be given to treat mild forms with minor bleeding in Hemophilia A.

A
  • desmopressin

- fibrinolytic inhibitors

80
Q

Complications of Hemophilia A include:

A

joint disease
pseudotumors (hematomas)
fatal hemorrhage

81
Q

This disease is due to decreased production of Factor IX.

A

Hemophilia B

82
Q

Clinically, Hemophilia B is similar to Hemophilia A except for which lab values?

A

Factor IX will be decreased (VIII will be normal)

83
Q

This refers to a decrease in platelet count (<100,000/uL).

A

Thrombocytopenia

84
Q

Evaluation of thrombocytopenia is made using ________ information and peripheral _______ smear morphology.

A

clinical

blood

85
Q

Name a few conditions that can result in increased destruction of platelets.

A
immune-mediated conditions
sepsis
DIC
TTP
vasculitis
burns
drugs
fat emboli
hemorrhage
86
Q

This disorder is characterized by immune-mediated destruction of platelets.

A

Immune Thrombocytopenic Purpura (ITP)

87
Q

These are common targets of autoantibodies in the ITP disease process.

A

GP Ib/IX and IIb/IIIa

88
Q

The acute form of ITP occurs in ________ and is typically severe, while the chronic form is more typical in _______ with gradual onset.

A

childhood

adults

89
Q

Therapy of ITP includes:

A

corticosteroids
IV immunoglobulin
splenectomy

90
Q

This disorder is characterized by intravascular platelet activation with formation of platelet-rich micro thrombi throughout the circulation.

A

Thrombotic Thrombocytopenic Purpura (TTP)

91
Q

The cause of TTP is a deficiency of a _____________ ADAMTS 13, which normally degrades very-high-molecular-weight multimers of vWF.

A

metalloproteinase

92
Q

Deficiency of ADAMTS 13 results in accumulation of ____ in plasma.

A

vWF

93
Q

Classic manifestations of TTP include:

A
fever
marked thrombocytopenia
microangiopathic hemolytic anemia
acute renal failure
neurologic changes
94
Q

Labs of TTP patient will show thrombocytopenia, ________ in peripheral blood smear, anemia, reticulocytosis, ______ coagulation parameters, and _______ bilirubin and LD (intravascular hemolysis)

A

schistocytes
normal
increased

95
Q

Clinical manifestations of DIC include bleeding from _______ sites, thrombotic problems, hypotension/shock, and dysfunction in which systems?

A

multiple

respiratory, hepatic, renal, CNS

96
Q

What clinical situations increase risk of developing DIC?

A
bleeding/thromboembolic problems
dysfunction of organ system
infections (Gram negative)
tissue injury
OB complications
malignancies
venomous snake bites
vascular lesions
hemolytic transfusion reaction
97
Q

Therapy of DIC is directed at:

A

removing the initiating stimulus

support patient’ s coagulation protein reserve (transfusions of FFP and cryoprecipitates)