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Block 7 week 4 > Hemostasis and Disorders - Fung > Flashcards

Hemostasis and Disorders - Fung Flashcards

1
Q

What is hemostasis?

A

Defined as the balance between clotting and thrombosis.

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2
Q

Describe hemostasis.

A
  1. precisely orchestrated process involving platelets, clotting factors and endothelium
  2. occurs at the site of vascular injury and culminates in the formation of a blood clot
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3
Q

Name 2 broad categories of disorders of hemostasis.

A
  1. hemorrhagic disorders - characterized by excessive bleeding
  2. thrombotic disorders - characterized by clot formation
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4
Q

What are the general steps of normal hemostasis?

A
  1. vasoconstriction
  2. platelet aggregation
  3. fibrin formation
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5
Q

Describe hemostasis.

A
  1. vasoconstriction - a transient effect mediated by reflex neurogenic mechanisms. Basically causes reduced blood flow to area of injury and is augmented by local secretion of endothelin
  2. primary hemostasis - platelets circulating in blood adhere to endothelium and are activated. This process leads to platelet aggregation and is the beginning of a blood clot
  3. secondary hemostasis - tissue factor is exposed at the site of vascular injury which sets in motion a cascade of reactions that lead to thrombin formation
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6
Q

What are the 3 main layers of a blood vessel?

A
  1. tunica intima - contains endothelium
  2. tunica media - contains layers of smooth muscle
  3. tunica adventitia - contains a lot of connective tissue
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7
Q

What 2 blood vessel layers are involved in vasoconstriction?

A
  1. tunica adventitia

2. tunica media

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8
Q

Which layer of the blood vessel is actively regulating hemostasis?

A

The tunica intima contains endothelium which actively regulates hemostasis.

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9
Q

How does endothelium actively regulate hemostasis?

A
  1. inhibits platelets
  2. suppresses coagulation
  3. promotes fibrinolysis
  4. modulates vascular tone and permeability
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10
Q

What are some anti-thrombotic factors in blood vessels that help to maintain homeostasis?

A
  1. Heparin - blocks some coagulation factors
  2. Protien C and S
  3. Tissue plasminogen activator - plasminogen breaks down fibrin clots
  4. Prostacyclin - mediates vasodilation
  5. NO - mediates vasodilation
  6. thrombomodulin
  7. Protein C receptor
  8. Tissue factor pathway inhibitor
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11
Q

What are some prothrombotic factors in blood vessels that help maintain homeostasis?

A
  1. Factor V
  2. Tissue factor
  3. Plasminogen activator inhibitor-1
  4. thromboxane
  5. platelet activating factor
  6. vWF
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12
Q

What happens when there is vascular injury?

A
  1. tissue factor is released
  2. extracellular matrix (collagen ) is exposed
  3. tunica media and tunica adventitia mediate vasoconstriction
  4. exposure of collagen and vWF sets the stage for platelet adherence and activation - platelets adhere to vWF and collagen and are activated
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13
Q

What happens when platelets are activated?

A
  1. they first bind at the site of tissue injury to vWF (via GPIb/V/IX) and collagen
  2. upon binding they will change shape and their fibrinogen receptors are activated (GP IIb/IIIa), allowing cross-linking of platelets
  3. they will degranulate, releasing the contents of the alpha and dense granules and will recruit other platelets
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14
Q

Where do platelets come from?

A

They are derived from megakaryocytic maturation. They are a nucleate structures consisting of a cytoskeleton and cytoplasmic granules.

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15
Q

Describe platelets.

A
  1. derived from megakaryocytic
  2. anucleate
  3. cytoplasm contains granules - alpha and dense granules
  4. have a cytoskeleton that has glycoproteins that function in platelet adherence
  5. membrane has ABO antigens, HLA antigens and other antigens
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16
Q

What glycoprotein located in the cytoskeleton of platelets allows the platelet to bind to vWF?

A

The glycoprotein 1b/V/IX.

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17
Q

Name some other important glycoproteins on platelets that are important.

A
  1. GP IIb/IIIa - binds to fibrinogen. Fibrinogen allows platelets to crosslink and form a clot
  2. GP Ic/IIa - binds fibronectin
  3. thrombin receptor - initates platelet activation when bound by thrombin
  4. ADP receptor - initiates platelet activation when bound by ADP. ADP is inside dense granules and when released it recruits additional platelets to site of injury
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18
Q

What are the constituents of alpha granules?

A
  1. vWF
  2. fibrinogen
  3. Factor V
  4. VEGF, EGF,PDGF
  5. angiostatin, thrombospondin, endostatin
  6. PF-4, IL-8, CCL5
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19
Q

What factors of alpha granules promote angiogenesis?

A
  1. VEGF, EGF,PDGF
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20
Q

What factors of alpha granules inhibit angiogenesis?

A
  1. Angiostatin
  2. thrombospondin
  3. endostatin
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21
Q

What are the constituents of dense granules?

A
  1. ATP
  2. ADP
  3. calcium
  4. Serotonin
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22
Q

Are fibrinogen receptors on platelets active when they are circulating?

A

No. The receptors will become activated when platelets bind to vWF and change shape.

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23
Q

What are 2 ways that granule release leads to recruitment of more platelets?

A
  1. release of ADP - binds to and activates other platelets

2. activation of the thromboxane A2 pathway - leads to recruitment of more platelets

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24
Q

What happens during primary homeostasis and secondary hemostasis?

A
  1. in primary hemostasis platelets are binding and becoming activated and starting to aggregate
  2. in secondary hemostasis - the coagulation cascades are activated
  3. primary and secondary hemostasis happen at the same time
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25
Q

What are the 3 pathways that lead to coagulation?

A
  1. intrinsic pathway
  2. extrinsic pathway
  3. common pathway
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26
Q

Do the different coagulation pathways occur at different times?

A

No. They all occur together to cause coagulation.

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27
Q

Describe the Extrinsic pathway.

A
  1. tissue factor cleaves inactive factor VII to active factor VIIa
  2. factor VIIa feeds into the common pathway - it cleaves inactive Factor X into active factor Xa
  3. the rest of the common pathway occurs and a blood clot forms
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28
Q

Describe the common pathway.

A
  1. factors from the extrinsic pathway, intrinsic pathway and other pathways lead to the inactive factor X being cleaved to the active factor Xa
  2. factor Xa cleaves inactive prothrombin or factor II into the active thrombin or factor IIa
  3. thrombin cleaves the inactive fibrinogen to the active fibrin
  4. fibrin is cross linked and a clot is formed
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29
Q

Describe the intrinsic pathway.

A
  1. the close proximity of prekalikrein, high molecular weight kininogen and factor XII cause the inactive factor XII to be cleaved to the active XIIa
  2. factor XIIa cleaves the inactive XI into the active XIa
  3. factor XIa cleaves the inactive factor IX to the active factor IXa
  4. factor IXa feeds into the common pathway by acting on factor X
  5. the common pathway results in a clot
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30
Q

How can the Extrinsic pathway feed into the Intrinsic pathway?

A

Factor VII can cleave inactive factor IX to the active IXa which feeds into the common pathway by acting on factor X.

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31
Q

What are some other ways that the common pathway or parts of the common pathway can be activated?

A
  1. factor VIII is cleaved into active VIIIa and forms a complex with Xa and calcium that activates prothrombin to thrombin. This is called the tenase complex
  2. factor XIII is cleaved into active XIIIa which then causes fibrin to cross link
  3. factor Va can form a complex with Xa that leads to inactive prothrombin being cleaved into active thrombin. This is called the prothrombinase complex
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32
Q

Where are factors I-XIII made?

A

In the liver.

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33
Q

Where is vWF made?

A

In the endothelial cells and megakaryocytes.

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34
Q

Where is Prekalikrein and high molecular weight kininogen made?

A

In the liver.

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35
Q

What factors are vitamin K dependent?

A
  1. factor II
  2. factor VII
  3. factor IX
  4. factor X
    In order for these factors to bind the required calcium they have to be carboxylated. vitamin K carboxylates them and then is regenerated.
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36
Q

What is another name for factor I?

A

fibrinogen

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37
Q

What is another name for factor II?

A

prothrombin

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38
Q

What is another name for factor VIII?

A

antihemophilic factor

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39
Q

What is another name for factor IX?

A

Christmas factor

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40
Q

What is another name for factor XII?

A

Hagemann factor

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41
Q

What is another name for factor XIII?

A

fibrin stabilizing factor

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42
Q

What is another name for vWF?

A

von Willebrand factor

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43
Q

Most factors require 10-30% percent activity for normal coagulation. Which ones require less than 5%?

A
  1. factor XII
  2. factor XIII
  3. Prekalikrein
  4. high molecular weight kininogen
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44
Q

What are the half-lives of the different factors?

A 
I - 100-150 hs
II - 50-80 hs
V - 24 hs
VII - 6 hs
VIII - 12 hs
IX -24 hs
X - 25-60 hs
XI - 40-80 hs
XII - 50-70 hs
XIII - 150 hs
vWF - 24 hs
Prekalikrein - 35 hs
HMW kininogen - 150 hs
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45
Q

What are some substances that regulate coagulation and what factors do they inhibit?

A
  1. Antithrombin inhibits - thrombin, IXa, Xa, XIa and XIIa
  2. Activated protein C inhibits - Va, VIIa
  3. Tissue factor pathway inhibitor/extrinsic pathway inhibitor inhibits - tissue factor, VIIa and Xa
  4. Plasmin degrades fibrin (tissue plasminogen activator converts plasminogen to plasmin)
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46
Q

What is activated protein C?

A

A complex of thrombin, thrombomodulin, protein C and protein s. This complex inhibits factor Va and factor VIIa.

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47
Q

What is another mechanism of regulation of coagulation?

A

Feed back inhibition. Thrombin will feed back and inhibit the conversion of factor V to factor Va and factor VIII to factor VIIIa.

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48
Q

What two broad categories are evaluated when doing a lab evaluation of homeostasis?

A
  1. platelets

2. coagulation cascade

49
Q

What is bleeding time in reference to platelet evaluation?

A

Bleeding time is a factor that is evaluated when screening for qualitative platelet disorders or von Willebrand disease. This test is only used in patients with a history of excessive bleeding.

50
Q

What is the normal range for bleeding time?

A

1.5-9.5 minutes

51
Q

When is bleeding time prolonged?

A
  1. aspirin ingestion
  2. uremia
  3. platelet counts of less than 100,000
  4. with von Willebrands disease
  5. with inherited platelet disorders
52
Q

What is platelet aggregometry?

A
  1. in vitro evaluation of platelet aggregation
  2. performed on platelet rich plasma that is exposed to various agents
  3. the agents are - ADP, epinephrine, arachidonate, collagen and ristocetin (another name for vWF)
53
Q

Describe how flow cytometry is used in platelet evaluation.

A
  1. detects cell surface proteins with fluorescently labeled antibodies
  2. used to diagnose deficiencies of platelet surface glycoproteins and disorders of platelet activation
54
Q

What is a platelet count?

A

Platelet count is the number of platelets in a mL of blood. The count is determined by an automated counter. The reference range is 140,000-400,000 cells per mL of blood.

55
Q

What is Prothrombin time (PT)?

A

This is a method of evaluating the extrinsic and common pathways. Tissue factor and thromboplastin are added to plasma with excess calcium and the time to clot is measured. The reference range is 11-13.5 seconds.

56
Q

When is PT prolonged?

A

This can happen when there are deficiencies in or antibodies against:

  1. factor VII
  2. factor X
  3. factor V
  4. factor II (prothrombin)
  5. fibrinogen
57
Q

How does Coumadin affect vitamin K?

A

Coumadin prevents vitamin K from being regenerated (to reduced form) after it carboxylates factors II, VII, IX, X, protein C and protein s. This prevents clotting.

58
Q

PT time is also used to evaluate what?

A

It is used to monitor patients on coumadin therapy.

59
Q

activated partial thromboplastin time (aPTT) is used to evaluate what?

A
  1. used to evaluate the intrinsic and common pathways
  2. phospholipid is added to plasma with excess calcium and the time to clot is measured
  3. reference range is 27-35 seconds
  4. used to monitor Heparin, Hirudin or Argatroban therapy
60
Q

A prolonged aPTT would indicate what?

A

It would indicate a deficiency in or antibodies against the factors involved in the intrinsic and common coagulation cascade. Including:

  1. factor XII
  2. factor IX
  3. factor X
  4. factor II
  5. factor XI
  6. factor VII
  7. factor V
  8. fibrinogen
61
Q

What is Thrombin time used to evaluate?

A
  1. used to test the presence of functional fibrinogen
  2. thrombin is added to patient’s plasma and time to clot is measured
  3. reference range is 15-19 seconds
62
Q

Prolonged Thrombin time indicates what?

A
  1. Heparin
  2. Hirudin
  3. Argatroban
  4. dysfibrinogenemia
63
Q

In what situation would you perform a mixing study?

A
  1. mixing studies involve mixing a patient’s plasma with normal test plasma in a 1:1 ratio, you also must exclude the presence of heparin through heparin neutralization
  2. it is used to evaluate the cause of prolonged clotting times - PT, PTT, TT
  3. it is used to screen for the presence of inhibitors or antibodies against coagulation factors
64
Q

How do you interpret the results of a mixing study?

A

Basically, if there is any activity or clotting then that means that there are no inhibitors present in the pt’s plasma - the problem must be with the clotting factors themselves.
If there is at least 50% activity, prolongation is due to a factor deficiency
If there is less than 50% activity then prolongation is due to the presence of an inhibitor

65
Q

What is a D-dimer test?

A
  1. D-dimers are formed by plasmin mediated degradation of fibrin
  2. the presence of D-dimers indicates that fibrin has been formed and degraded - it is a sign that coagulation has taken place
66
Q

What is a von Willebrand factor assay?

A
  1. also called a Ristocetin cofactor assay
  2. is a version of platelet aggregation where the patient plasma is added to formalin-fixed normal platelets in the presence of ristocetin
  3. normal platelets will have platelet agglutination
  4. vWF deficient patients will have decreased aggregation
67
Q

What other assays are available to test coagulation factors?

A
  1. Anti-Xa assay - used to monitor either unfractionated or low molecular weight heparin use
  2. Individual factor assays - done after an initial mixing study that shows that there is a factor deficiency
  3. Factor VIII assay - this factor is associated with Hemophilia
  4. Fibrinogen activity
  5. Protein C activity
  6. Protein S activity
68
Q

What does Heparin do?

A

It potentiates the action of antithrombin. Factor Xa is inhibited by antithrombin so you would monitor factor Xa to see how Heparin is working.

69
Q

What is hemophilia?

A

Excessive bleeding.

70
Q

What two broad categories may be involved in bleeding disorders?

A
  1. platelet -type bleeding disorders

2. coagulation-type bleeding disorders

71
Q

Name some things you may see in coagulation-type bleeding disorders?

A
  1. Hemarthroses
  2. deep hematomas
  3. delayed bleeding
  4. usually affects males because these types of disorders are more often X-linked
72
Q

What is rarely seen in coagulation-type bleeding disorders?

A
  1. petechiae

2. mucosal bleeding

73
Q

Name some things you may see in platelet-type bleeding disorders?

A
  1. petichiae
  2. mucosal bleeding
  3. occurs in females mainly
74
Q

What is rarely seen in platelet-type bleeding disorders?

A
  1. hemarthroses
  2. deep hematomas
  3. delayed bleeding
75
Q

Name some platelet-type bleeding disorders.

A
  1. von Willebrand’s disease
  2. Bernard Soulier syndrome
  3. Glanzmann thrombastenia
  4. platelet storage pool disorders
  5. drug- induced
  6. immune thrombocytopenic purpura (ITP)
  7. thrombotic thrombocytopenic purpura (TTP)
  8. hemolytic uremic syndrome (HUS)
  9. Heparin induced thrombocytopenia (HIT)
76
Q

Name some coagulation-type bleeding disorders.

A
  1. von Willebrand’s disease
  2. Hemophilia A
  3. Hemophilia B
  4. Liver disease
  5. Vitamin K deficiency
  6. DIC - disseminated intravascular coagulation
77
Q

Why id von Willebrand’s disease both a platelet- type and coagulation-type bleeding disorder?

A

von Willebrand’s factor binds to platelets and it also binds to circulating factor VIII. It increases the half-life of factor VIII in serum by binding so lack of vWF would lead to deficiency in factor VIII.

78
Q

Describe von Willibrand disease as it applies to platelet-type bleeding disorders.

A
  1. defect in platelet adhesion
  2. most common inherited bleeding disorder
  3. combined platelet and coagulation defect so patient presents with symptoms of both types
  4. four main types - Type I, Type II (a,b,M,N), Type III (severe disorder with no vWF), Pseudo (platelet type with abnormal GPIb leading to increased binding of vWF)
79
Q

Describe von Willebrand Factor.

A
  1. synthesized in endothelial cells and megakaryocytic
  2. stored in Weibel-Palade bodies of endothelial cells and alpha granules of megakaryocytic
  3. mediates platelet adhesion via GPIb
  4. circulates as variably sized multimers
  5. complexes with factor VIII in circulation
  6. vFW activity also referred to as ristocetin cofactor activity
80
Q

Describe vWb disease Type I.

A
  1. most common type
  2. causes mild bleeding disorder
  3. quantitative disorder showing reduced amounts of vWF
81
Q

What are the laboratory findings of vWb disease Type I?

A
  1. normal PT
  2. prolonged PTT and bleeding time
  3. decreased factor VIII - because it prolongs half life of VIII when bound
  4. decreased vWF and activity
82
Q

Describe von Willebrand disease Type II.

A
  1. qualitative deficiency in vWF

2. 4 subtypes

83
Q

Describe vWb disease Type IIa.

A
  1. moderately severe
  2. involves absence of high molecular weight multimers
  3. will see slightly prolonged PTT due to less Factor VIII
  4. normal PT, TT times
  5. fibrinogen normal
  6. Ristocetin cofactor activity is decreased
  7. factor VIII and vWF normal to decreased
84
Q

Describe vWb disease Type IIb.

A
  1. results from spontaneous binding of vWF to platelets
  2. decreased high molecular wight multimers
  3. will see increased or enhanced ristocetin cofactor activity
  4. do not treat with DDAVP - may cause profound thrombocytopenia and bleeding
85
Q

What is the main laboratory difference seen with vWb disease Types IIa and IIb?

A

There will be decreases Ristocetin cofactor activity in Type IIa and increased activity in Type IIb.

86
Q

Descrobe vWb disease Type IIM and Type IIN.

A
  1. type IIM - rare defect that prevents vWF binding to GPIb

2. type IIN - rare defect with reduced vWF binding to FVIII

87
Q

Describe Bernard Soulier syndrome.

A
  1. defect in platelet adhesion due to decreased GPIb/V/IX (receptor for vWF)
  2. patients clinically manifest with thrombocytopenia and giant platelets
  3. platelet function tests will show aggregation with all agonists except Ristocetin
88
Q

How can you tell the difference between von Willebrand disease and Bernard Soulier syndrome?

A

Platelet function tests will be similar but on peripheral smear you will see large platelets.

89
Q

Describe Glanzmann thromboasthenia.

A
  1. autosomal recessive disorder due to deficient GPIIb/IIIa (fibrinogen receptor)
  2. platelets lack the PL(A1) antigen
  3. platelets will fail to aggregate with all agonists except Ristocetin in a platelet function test
90
Q

Describe platelet storage pool defects.

A
  1. Dense granule disease - due to lack of second wave aggregation. Associated with Hermansky-Pudick disease, Chediak-Higashi disease and Wiskott-Aldrich disease.
  2. Alpha-granule disease - platelet aggregation is blunted with all agonists except ADP in platelet function test because ADP is a constituent of dense granules. Associated with Gray platelet syndrome.
91
Q

How can Aspirin and NSAIDs lead to excessive bleeding?

A
  1. these are COX-1 inhibitors (COX-1 is enzyme involved in thromboxane A2 production)
  2. thromboxane A2 stimulates platelets so that dense granules are released and there is a secondary wave of aggregation
  3. Aspirin binds covalently so its effects are irreversible
  4. NSAID effects are reversible
92
Q

How can use of Ticlopidine and Clopidogrel lead to excessive bleeding?

A
  1. cause inhibition of ADP-mediated platelet activation

2. will see blunted platelet aggregation on platelet function tests in response to ADP

93
Q

How can use of Abciximab, Eptifibatide, and Tirofiban lead to excessive bleeding?

A
  1. inhibitors of GP IIb/IIIa (fibrinogen receptor)

2. will see impaired aggregation to all agonists except Ristocetin in platelet function test

94
Q

Which excessive bleeding disorders are characterized by thrombocytopenia?

A
  1. immune thrombocytpenic purpura
  2. thrombotic thrombocytopenic purpura
  3. hemolytic uremic syndrome
  4. heparin induced thrombocytopenia
95
Q

Describe ITP.

A
  1. immune thrombocytopenic purpura
  2. caused by antibodies to platelet antigens
  3. antigenic target varies - GPIIb, GPIIa, GPIb, GPV
  4. diagnosis of exclusion - healthy patient with isolated thrombocytopenia with no obvious cause
96
Q

Describe TTP.

A
  1. thrombotic thrombocytopenic purpura
  2. syndrome resulting from widespread formation of microvascular platelet thrombi
  3. thrombi can effect CNS, kidneys, GI tract and other organs
  4. presents with pentad of symptoms - thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities, renal abnormalities and fever
97
Q

What is the pathogenesis of TTP?

A
  1. acute deficiency of vWF- cleaving metalloprotease called ADAMTS13
  2. causes an accumulation of ultra large vWF multimers which bind platelets and lead to both thrombi in the microvasculature and thrombocytopenia
  3. usually idiopathic and isolated event in which antibodies are made to the enzyme ADAMT13
98
Q

Describe HUS.

A
  1. hemolytic uremic syndrome
  2. thrombotic microangiopathy characterized by thrombocytopenia, acute renal failure and microangiopathic hemolytic anemia
  3. most commonly associated with bloody diarrhea caused by shiga-toxin producing bacteria such as S. dysenteriae or E. coli O157:H7
99
Q

Describe HIT.

A
  1. heparin induced thrombocytopenia
  2. occurs in 1-3% of patients treated with unfractionated heparin for greater than 5 days
  3. an immune mediated disorder caused by IgG antibodies against the complex of heparin and PF4
  4. although thrombocytopenia occurs, bleeding is rare and thrombosis is more common
  5. thrombosis is likely due to platelet aggregation and activation of coagulation
  6. symptoms include thrombocytopenia, thrombosis, and allergic reactions
100
Q

Describe Hemophilia A.

A
  1. due to congenital X-linked recessive deficiency of Factor VIII
  2. results in decreased or absent circulating factor VIII resulting in lifelong bleeding
  3. presents with delayed bleeding and joint and muscle bleeding
  4. will see increased PTT
  5. normal platelet count
  6. normal PT and TT
  7. decreased plasma factor VIII assay
101
Q

Describe Hemophilia B.

A
  1. due to a congenital X-linked recessive deficiency of factor IX
  2. results in decreased or absent factor IX leading to lifelong bleeding
  3. also known as Christmas disease
  4. similar to Hemophilia A - delayed bleeding and joint and muscle bleeding
  5. will see prolonged PTT
  6. normal PT and TT
  7. decreased factor IX assay
102
Q

How can you tell the difference between Hemophilia A and B?

A

Clinically, they will be indistinguishable but when doing lab evaluation you can do an individual factor assay.

103
Q

How can liver disease lead to excessive bleeding?

A
  1. decreased synthesis of most clotting factors including fibrinogen
  2. chronic DIC due to impaired clearance of D-dimer (D-dimer stimulates coagulation)
  3. will see prolonged PT
  4. will see prolonged TT
104
Q

How can vitamin K deficiency lead to excessive bleeding?

A
  1. vitamin K is involved with carboxylation of Gla domains of clotting factors
  2. deficiency lead to impaired production of the vitamin K dependent factors - II, VII, IX, X, protein C and protein s
  3. vitamin K deficiency can be caused by hemorrhagic disease of the newborn (newborns do not have functioning vit K), antibiotics (decrease gut flora), malabsorption/malnutrition (vit K is fat-soluble) and Warfarin therapy
105
Q

Describe DIC.

A
  1. disseminated intravascular coagulation
  2. acquired syndrome characterized by intravascular activation of coagulation
  3. causes include - endotoxin causing sepsis, trauma, burns, obstetrical complications, vascular malformations, animal venom and mucin -secreting adenocarcinoma
  4. due to excess or prolonged exposure to tissue factor leading to generalized activation of coagulation system and thrombin generation
  5. fibrin formation and fibrinolysis cause micro thrombi and consumption of clotting factors and platelets
  6. there is no activation of tissue factor inhibitor due to ongoing exposure to tissue factor
106
Q

What are possible clinical manifestations of DIC?

A

The clinical findings vary according to inciting event.

  1. hemorrhage
  2. renal dysfunction
  3. hepatic dysfunction
  4. respiratory dysfunction
  5. shock
  6. CNS dysfunction
  7. petechiae
  8. purpura
  9. skin necrosis
  10. signs of thrombosis
107
Q

How do you evaluate for DIC?

A
  1. does pt have underlying condition associated with DIC?
  2. if yes, then order coagulation tests
  3. score the coagulation test
108
Q

How do you score the coagulation tests when evaluating for DIC?

A
  1. platelet count - if greater than 100,000 score is zero, if less than 100,000 score is one, if less than 50,000 then score is 2
  2. prolonged PT - if greater than 3-6 seconds then score is one, if greater than 6 seconds then score is 2, if less than 3 seconds then score is zero
  3. fibrinogen - if amount is greater than 100 mg/dl then score is zero, if less than 100 mg/dl then score is one
  4. fibrin monomers of degradation products (D-dimer) - if no increase then score is zero, if moderate increase then score is 2, if strong increase then score is 3
  5. if the overall score is greater to or equal to 5 then this is compatible with overt DIC, if less than 5 then not affirmative
109
Q

What is thrombophilia?

A

Excessive thrombosis.

110
Q

What are the two main types of thrombosis?

A
  1. arterial

2. venous

111
Q

Give some examples of conditions in which thrombophilia may be present.

A
  1. activated protein C resistance (Factor V Leiden)
  2. antithrombin deficiency
  3. antiphospholipid syndrome
  4. prothrombin variant
  5. protein C or protein s deficiency
112
Q

Describe Activated protein C resistance (APCR).

A
  1. inherited autosomal dominant condition responsible for 50% of the cases of hereditary thrombophilia
  2. due to point mutation in the FV gene that makes Factor V Leiden resistant to proteolytic cleavage by APC
  3. heterozygotes have 5-10% increased risk of thrombosis
113
Q

Describe antithrombin deficiency.

A
  1. autosomal dominant disorder characterized by recurrent venous thrombosis
  2. no inactivation of Factors II, IXa, Xa, XIa and XIIa
  3. heterozygotes have 5-10% increased risk of thrombosis
  4. homozygosity is considered incompatible with life
114
Q

Describe Antiphospholipid syndrome.

A
  1. an autoimmune thrombophiliccondition in which patients have circulating antibodies against plasma proteins that bind to phosophlipids
  2. patients present with recurrent arterial and venous thrombosis, pregnancy losses and immune cytopenias
  3. the antibodies are directed towards Beta2 glycoprotein, prothrombin and others
  4. primary APL occurs in healthy individuals
  5. secondary APL can occur with Systemic lupus, HIV, malignancy, drugs and collagen vascular disease
115
Q

What drugs are associated with secondary APL?

A
  1. phenytoin
  2. quinidine
  3. hydralazine
  4. procainamide
  5. phenothiazines
  6. IFN
  7. cocaine
116
Q

Describe Prothrombin variant G20210A.

A
  1. autosomal dominant condition due to a point mutation in the prothrombin gene
  2. mutation enhances prothrombin gene transcription leading to evaluated levels of prothrombin and thus thrombin
  3. second most common cause of inherited thrombophilia
117
Q

Describe Protein C/s deficiency.

A
  1. inherited autosomal dominant form with heterozygotes with 5-7 fold increased risk of thrombosis
  2. acquired form may result from coumadin therapy, liver disease and pregnancy
  3. deficiency can either be due to qualitative or quantitative defects
118
Q

What does Protein C do?

A

It inactivates factor V and factor VIII. Protein s is a cofactor for protein C and both are vitamin K dependent.

Block 7 week 4 (6 decks)

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