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Flashcards in Coagulation Deck (31)
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1

Coagulation part II Bleeding

Coagulation part II Bleeding

2

What are the defects and genetic inheritance in the following illnesses...

 von Willebrands disease?

Hemophilia A

Hemophillia B

Hemophillia C

 

von Willebrands disease >> vWF; auto dom or auto Rec

Hemophilia A >> VIII; X-linked

Hemophillia B >> IX: X-linked

Hemophillia C >> XI: auto recessive

3

What are the causes to the following acquired disorders...

Blood loss?

Excess anticoagulation?

Disseminated Intravascular Clotting?

Inhibitors?

Blood loss >> platelet and clotting factor depletion

 

Excess anticoagulation >> inhibition of clotting factors

Disseminated Intravascular Clotting >> platlet or clotting factor consumption; excess fibrinolysis

 

Inhibitors >> antibodies to clotting factor usu. VIII

4

What is glycoprotein 1b?

 is a component of the GPIb-V-IX complex on platelets.

The GPIb-V-IX complex binds von Willebrand factor, allowing platelet adhesion and platelet plug formation at sites of vascular injury.


It is deficient in the Bernard-Soulier syndrome. A gain-of-function mutation causes platelet-type von Willebrand's disease.

5

What is von Willibrand Disease?

Dec/ Absent or abnormal VW multimers
S/S epistaxis (nose bleed), bruising, menorrhagia, GI, gingival bleeding
Classified into 3 types
Dx: BT bleeding time, FVIII, VWAg, RIPA
Rx: DDAVP

VWF binds to VIII

DDAVP: (desmopressin acetate) are a synthetic analogue of the natural pituitary hormone 8-arginine vasopressin (ADH), an antidiuretic hormone affecting renal water conservation.

6

What is Bernard Soulier Syndrome?

Deficiency of GP IB, Auto Recessive
Early childhood bruising, mucosal bleeding
Dx: Increased bleeding time, giant platelets, thrombocytopenia, Aggregation studies
Rx : platelets, DDAVP

7

What is Glanzmann's Thrombasthenia?

See slide 50

Auto Recessive

Deficiency of glycoprotein IIb/IIIa

symptoms: early childhood bruising and bleeding

DX: bleeding time BT, platelet aggregation studies

8

What is glycoprotein IIb/IIIa?

In medicine, glycoprotein IIb/IIIa is an integrin complex found on platelets. It is a receptor for fibrin[1] and aids in platelet activation. 

9

10

What is Virchow's triad?

Endothelial injury

Abnormal blood flow

Hypercoagulability

11

What are the examples of endothelial injury?

Heart: endothelial injury adjacent MI, valvulitis


Atherosclerotic ulcerated plaques, vasculitis


Endothelial injury due to bacterial endotoxins,  radiation, cigarette smoke products


End product: exposure of sub-endothelial collagen, platelet activation, adherence…..

12

What are examples in normal blood flow?

  • Turbulance; arterial and cardiac thrombosis
  • Stasis ; venous thrombosis
  • Mechanisn:
    • Disrupt laminar flow
    • Prevent dilution of activated factors by fresh flowing blood
    • Retard clotting factors inhibitors
    • Promote endothelial cell activation
  • Ulcerated atherosclerotic plaques, aneurysms-local stasis, MI, Mitral valve stenosis.

13

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14

What is activated protein C resistance?

Activated Protein C cannot inactivate V, and V stays in circulation longer.

See below for details

 

AA replacement at one of three APC cleavage sites in the factor Va molecule
Factor V Leiden inactivated ~ ten times slower than normal factor V
Persists longer in the circulation results in increased thrombin generation and a mild hypercoagulable state
Individuals heterozygous for the factor V Leiden mutation have a slightly increased risk for venous thrombosis; homozygous individuals have a much greater thrombotic risk

15

What happens with a 20210 mutation?

causes increased prothrombin

increases risk for thrombosis

16

What are the main risk factors for Hereditary Thrombophillia?

(don't need to know)

Factor V Leiden 30%

Prothrombin 8%

high homocysteine

 

17

What is Disseminated Intravascular Coagulation?

  • pathologic, consumptive coagulopathy
  • widespread, inappropriate coagulation leads to thrombosis of microvessels
  • consumption of procoagulants and excess plasmin generation leads to hemorrhage
  • Laboratory findings...

thrombocytopenia
prolonged screening coagulation tests
elevated D-dimer (fibrin degradation)
fragmented red blood cells (schistocytes)

18

What are the clinical causes of Disseminated Intravascular Coagulation?

bacterial sepsis, overwhelming viremia
trauma, tissue necrosis
some malignancies (esp. promyelocytic leukemia)
obstetric accidents
others

19

What is the treatment for DIC?

treat underlying condition
support with blood products
break DIC “cycle” with heparin (in some diseases)

20

What is heparin-induced Thrombocytopenia?

 
  • Unfractionated heparin preparations
  • Mechanism: generation of antibodies that bind Platelet Factor 4 PF4
  • Antibodies bind to heparin-like molecules present on platelet surface and endothelium
  • Platelet activation or endothelial injury occurs
  • Prothrombotic state
  • Tx: stop heparin

21

What is Antiphospholipid Antibody Syndrome aka Hughes Syndrome?

  • Essentially, the pt can form clots anywhere
  •  
  • Definition: Positive antiphospholipid antibody ; persistent, at least 6 weeks apart + 1 Clincial finding, such as
    • Arterial or venous thrombosis
    • Thrombocytopenia
    • Frequent miscarriages
  • Two classifications-
    • Secondary APS; underlying autoimmune disorder, such as SLE (systemic lupus erythemia)
    • Primary APS; No known underlying autoimmune disorder

22

Antiphospholipid Antibody Syndrome...

Mechanism?

Clinical Findings?

Dx?

Tx?

This is a long list. I doubt you need to know if.

Mechanism of hypercoaguable state: unknown
Direct platelet activation
Inhibition of PGI2 by endothelial cells
Inhibit functions of Protein C or S

CF : protean ; depending on vascular bed
Venous thrombosis: LE, Cerebral Vein, retinal
Neurologic disease: stroke , dementia
Preg complications: Miscarriages, HELLP
Hypoprothrombinemia

Diagnosis: Anticardiolipin Abs,  Lupus inhibitor

Treatment: Warfarin, heparin, steroids

23

Summary: 

Bleeding Disorders:
Vessel wall related abnormalities
Primary hemostasis (VW D, Bernard-Soulier, Glanzman Thrombasthenia
Secondary Hemostasis (Hemophilia, Christmas Disease)

Thrombosis- Virchows triad- endothelial abnormalities, hypercoagulable states

Summary:

Bleeding Disorders:
Vessel wall related abnormalities
Primary hemostasis (VW D, Bernard-Soulier, Glanzman Thrombasthenia
Secondary Hemostasis (Hemophilia, Christmas Disease)

Thrombosis- Virchows triad- endothelial abnormalities, hypercoagulable states

24

What are screening tests of Hemostatis?

  • Personal/Family History/PE**
  • First Level Testing:
  • Platelets:
    • Platelet count
    • Bleeding Time
  • Plasmatic Coagulation Factors
    • Prothrombin time (PT)
    • Activated Partial thromboplastin time(APTT)

25

What is the point of the Bleeding Time Dx technique?

What are its caveats?

  • Vascular component ( endothelium)
  • Platelet ( Qualitative/quantitative)
    • Congenital
    • Acquired ( Medications, autoimmune disorders, malignancies)

CAVEATS
Poor predictive value for hemostatic problems during surgery
Does not correlate in a linear fashion with platelet dysfunction
Not useful Dx/exclusion Bleeding diathesis
Useful DX pts with bleeding history

26

What is the point of the Platelet Count Dx technique?

Quantitative/Quantitative defects lead to bleeding problems
Myeloproliferative disorders elevated platelet ->Thrombosis or bleeding

27

What is the point of the PT screening tests?

Prothrombin Time

What is normal PT?

What prolongs PT?

What is an application of PT?

PT: 12-14 seconds

Prolonged by
Deficiencies of VII, X, V, II, fibrinogen
Inhibitors (D-dimer, paraprotein, lupus anticoagulant


Application
Warfarin (interferes with Vit K dependent factors (2,7,9,10) : Prolongs PT
PT can be used to monitor warfarin therapy
 

28

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29

What is the Int'l Normalized Ratio (INR)?

each thromboplastin has a different effect on PT

The higher ISI the less sensitive the reagent

INR=(patient PT/mean normal PT) ISI

Example:

reagent A (ISI=1.0) PT=41sec, MNPT=13.0, INR=3.1
reagent B (ISI=1.6) PT=26sec, MNPT=13.1, INR=3.1

30

What is the aPTT?

activated partial thromboplastin time.

Prolonged by?

 

Prolonged by

Deficiencies in VIII, IX, XI, XII, (HMWK,pre-kallikrein);

inhibitors...

heparin (unfractionated; less sensitive to LMWH)
lupus anticoagulant
specific acquired factor inhibitor (esp. VIII)