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Heme/Lymph > Defects of Coagulation mechanism > Flashcards

Defects of Coagulation mechanism Flashcards

1
Q

What are the 3 main types of bleeding disorders?

A

acquired platelet defects
inherited bleeding disorders
acquired coagulopathy

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2
Q

What is hemostasis?

A

process that prevents blood loss form damaged blood vessels

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3
Q

What is thrombosis?

A

pathological formation of a ‘hemostatic’ plug within the vascularture in the absence of bleeding
(excesive hemostasis)

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4
Q

What important factor is needed for platelet adhesion? Receptor?

A

vWF

GPIbalpha

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5
Q

What important factor is needed for platelet aggregation? Receptor?

A

Fibrinogen

GPIIb/IIIa

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6
Q

What is contained in dense granules in the platelet?

A

ADP, ATP
seratonin
calcium

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7
Q

What does calcium release lead to?

A

integrin activation

granule secretion

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8
Q

What are the 2 binding domains on vWF?

A

Gp1b

GPIIb/IIIa

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9
Q

What does binding of vWF with GP1b cause?

A

braking/activation of the platelet

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10
Q

What does binding of vWF ith GPIIb/IIIa cause?

A

arrest of the platelet

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11
Q

What does platelet granule release lead to?

A

signals other platelets

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12
Q

What does platelet membrane coagulant expression lead do?

A

thrombin and clot

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13
Q

Initiation phase of cell based coagulation

A

activaion of IXa & Xa

Xa converts II to IIa (thrombin)

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14
Q

Amplification phase of cell based coagulation

A

thrombin activated Va, VIIIa, XIa and platelets

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15
Q

Propagation of cell based coagulation

A

IXa catalyzing further thrombin formation

XIa augments by driving further IXa formation

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16
Q

Thrombin driven pahse of cell based coagulation

A

transformation of fibrinogen to fibrin and cross linking

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17
Q

What are the vitamin K dependent pro coagulant factors?

A

II, VII, IX, X

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18
Q

What are the vitamin K dependent anti coagulant factors?

A

Proteins C & S

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19
Q

What does thrombin activate?

A

Fibrinogen to fibrin
Factor XIIIz
TAF1

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20
Q

What does an intrinsic pathway deficiency lead to?

A

increased PTT

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21
Q

What does an extrinsic pathway deficiency lead to?

A

increased PT

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22
Q

What enzymes are important for the fibrinolytic system?

A

t-PA
Plasminogen
alpha-antiplasmin
D-dimer

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23
Q

What does active protein C do?

A

proteolysis of factors Va and VIIa

24
Q

What does mucosal bleeding usually indicate?

A

platelet defect of vWF

25
Q

What does deep tissue bleeding usually indicate?

A

factor deficiency

26
Q

Generalized oozing at venipuncture sites is indicative of?

A

DIC

27
Q

What are screening tests done for platelet phase problems?

A

platelet count

PFA-100

28
Q

What are screening tests done for coagulation phase problems?

A

PT
PTT
Fibrinogen
Inhibitor screening (1:1 mix)

29
Q

How do we check for quantitative defects of platelets?

A

peripheral blood film

Vit B12, PF4 ELISA

30
Q

What causes decreased platelet production?

A

vit B12 deficiency

marrow failure or disease

31
Q

What are peripheral destruction syndromes that can cause thrombocytopenia?

A 
DIC (non-immune)
Immune
-Fab mediated (ITP)
-Non-Fab mediated (heparin induced, TTP)
-innate immunity (sepsis)
32
Q

ITP types and features

A

childhood-abrupt, viral syndrome, autoantibody to platelet surface glycoproteins, most patients recover
adult-insidious, only 5% spontaneous recovery

both have large platelets

33
Q

HIT (heparin induced thrombocytopenia) features

A

immune disease, neo epitope (heparin:PF4) causes transient autoimmune disease (4-14 days into heparin tx)
moderate thrombocytopenia
associated with thrombotic events
confirm w/PF4-Heparin elisa
stop heparin, begin alternate anticoag tx

34
Q

Thrombotic microangiopathies

A

microangiopathic blood films

  • TTP
  • HUS
  • DIC
  • Sepsis
35
Q

TTP features

A 
microangiopathic hemolytic anemia
thrombocytopenia
renal failure
mental status change
fever
ADAMTS13
36
Q

What is the role of ADAMTS13?

A

regulates vWF/platelet interaction (cleaves vWF)

37
Q

How do you treat TTP?

A

plasma exchange

38
Q

What does PFA-100 screen for? measure?

A

screens for platelet and vWF function
measures occlusion time
sensitivity/specificity lower than desireable

39
Q

What are the functions of vWF?

A

supports platelet adhesion
carrier for factor VIII
abnormalities lead to long PTT

40
Q

Screening for vWF disease?

A

PFA-100
PTT
assay vWF

41
Q

What is bernard soulier syndrome?

A

congenital absence of GPIb

platelet function defect

42
Q

What is Glanzman’s thrombasthenia?

A

congenital absences of GPIIb/IIIa

platelet function defects

43
Q

How is a PT test performed?

A

Tissue factor, phospholipid and Ca2+ are added to citrated plasma and clotting time is measured

44
Q

What is INR?

A

normalized PT so that result is comparable across labs
intended for warfarin monitoring
(pts PT/mean normal PT)^ISI

45
Q

What is the 1:1 mix test?

A

pt plasma is mixed with normal plasma with all factors, clotting time is performed on mixed sample
if clotting time corrects to normal: factor def likely
if clotting time remains prolonged: “inhibitor” likely

46
Q

DDX of isolated long PTT?

A 
Factor deficiency
inhibitors present (heparin, lupus anticoag, specific factor inhibitor)
47
Q

DDX of isolated long PT?

A

Factor deficiency
-VII
_vit K defic, oral anticoag, liver disease

48
Q

What factors are not tested by screens?

A

Factor XIII

Anticoagulants (Proteins C&S, factor V leiden)

49
Q

Prolonged PT and PTT DDX?

A 
factor deficiency (isolated or combo [liver disease, vit K defic, DIC])
inhibitors present (isolated factor inhibitor, drugs, lupus inhibitor)
50
Q

What factor is deficient in Hemophilia A?

A

VIII

51
Q

What factor is deficient in Hemophilia B (christmas disease)?

A

IX

52
Q

How is hemophilia inherited?

A

X linked

53
Q

Sx of hemophilia?

A

hemarthrosis & deep muscle bleeds
prolonged PTT (corrects on 1:1 mix)
sx correleate with level

54
Q

Problems causing vitamin K deficiency?

A

drugs-oral anticoags (warfarin), antibiotics that decreased bowel flora (less vit K synthesis)
malabsorption or dietary deficiency
liver disease
newborns

55
Q

What occurs with liver disease in regard to anticoagulation?

A 
deficiency of multiple coag factors
-pro: II, VII, IX, X & V
-anti:antithrombin, protein C, protein S
thrombocytopenia
-hypersplenism
-decreased TPO production

Heme/Lymph (18 decks)

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