Drugs affecting hemostasis Flashcards

1
Q

What are the types of drugs that affect hemostasis?

A
Anticoagulants
Direct Thrombin Inhibitors
Heparin Antagonists
Hemostatics
Thrombolytic Agents
Platelet Inhibitors
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2
Q

Coagulation, along with fibrinolysis and wound healing are largely responsible for maintaining the circulation as a closed hemodynamic system in a normal basal state equilibrium, referred to as

A

Hemostasis

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3
Q

What is Virchow’s triad?

A

Hypercoagulable state
Vascular wall injury
Circulatory stasis

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4
Q

Damage outside blood vessels triggers the release of thromboplastin (Factor III, tissue factor) from damaged cells.

A

Extrinsic pathway

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5
Q

What activates factor VII?

A

Thromboplastin

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6
Q

Both the extrinsic and intrinsic pathways can activate which factor?

A

X

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7
Q

Thromboplastin activates factor ______, ______ when complexed on the surface of the platelet with calcium _________ and thromboplastin _____ activates factor__.

A

VII; VIIa; IV; IIIa; X

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8
Q

The extrinsic pathway is inhibited by . . .

A

Coumadin, PT/INR

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9
Q

Describe the Intrinsic pathway: Trauma to the blood activates factor ____ which activates factor ____ and activates factor _____, which when on the platelet surface activates factor _____ and calcium which activates factor ___.

A

XII; XI; IX; VIII:C; X

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10
Q

The intrinsic pathway is inhibited by. . .

A

Heparin; Aptt

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11
Q

Which factor is Calcium?

A

IV

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12
Q

Describe the Common Pathway: Factor Xa on the platelet surface with factor ___ and calcium converts ________ to Thrombin

A

V; Prothrombin (IIa)

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13
Q

Which factor converts fibrinogen to fibrin?

A

Prothrombin (IIa)

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14
Q

What occurs when factor XIII is present in the conversion of fibrinogen to fibrin?

A

cross-linking

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15
Q

What system and meds does the Bleeding time test?

A

Platelets and Capillaries; ASA, Plavix, Ticlid, poss. NSAIDs

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16
Q

What system and meds does the PT test?

A

Extrinsic, common pathways; Warfarin

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17
Q

What system and meds does the aPTT test?

A

Intrinsic, Common pathways; heparin

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18
Q

What system and meds does the TT (thrombin time) test?

A

Fibrinogen to Fibrin; Heparin

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19
Q

This med is an anionic, sulfated, glycosoaminoglycan found in the secretory granules of mast cells. . .

A

Heparin

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20
Q

Heparin acts as a _________ to accelerate the rate at which acti-thrombin III neutralizes _______ and factor ___.

A

catalyst; thrombin; Xa

21
Q

T/F Heparin comes from the Porcine intestinal mucosa and bovine lung

A

True

22
Q

WHat is the MOA for heparin?

A

it increases the rate of thrombinantithrombin III reaction at least 1000 fold by serving as a catalytic template to which both AT III and protease (thrombin) bind

23
Q

What are heparin’s uses?

A

Prophylaxis for: Venous thrombi, DVT and PE, Embolization from A.fib/prosthetic valve, peripheral artery embolism
DX and treatment of DIC
Angina, non Qwave MI, acute Mi and percutaneous coronary intervention
complications of pregnancy
-coagulation during arterial and cardiac surgery

24
Q

T/F heparin acts on Bound and Unbound factors

A

False, only on bound

25
Q

What is the onset time for Heparin?

A

IV immediate

SQ 1-2 hours

26
Q

How is Heparin metabolized?

A

It is cleared by the reticuloendothelial system

27
Q

How do you dose Heparin for CPB?

A

300-400 units/kg IV

Achieve an ACT >400 seconds

28
Q

Can you give Heparin to pregnant women?

A

Yes, it DOES NOT cross the BBB

29
Q

Why do those with Heparin Resistancy require higher doses to achieve desired aPTT or ACT?

A

Increased Factor VIII
accelerated clearance with massive PE
Inherited ATIII deviancy
ATIII with liver cirrhosis, nephrotic syndrome or DIC

30
Q

What are the TOxic effects of Heparin?

A

Bleeding
Thrombocytopenia
Abnormal LFTs
Infrequent risk of osteoporosis and spontaneous vertebral fractures

31
Q

What condition may occur 7-14 days after heparin therapy, possibly due to heparin dependent antiplatelet IgG antibodies or direct nonimmunogenic affect on PLts and in a majority of pts. associated with thrombotic complications including arterial thrombosis with platelet fibrin clots?

A

HITTS

32
Q

This heparin antagonist is a strongly basic protein made from the sperm of salmon and forms a stable salt

A

Protamine Sulfate

33
Q

What are the uses for Protamine?

A

Neutralize heparin after CPB procedures and others where higher molecular weight heparin was used for anticoagulation

34
Q

Are LMWHs susceptible to Protamine

A

No, if emergency reversal is needed, protamine will neutralize about 65% of Anti-Xa activity of LMWH

35
Q

How should you administer Protamine?

A

SLOW! IV 10mg/ml over 1-3minutes, 50mg/10mins maximum

36
Q

What are the adverse effects of Protamine?

A

Rapid injection is profound hypotension, bradycardia, Pulm.HTN, transcient flushing, dyspnea
Watch BP, AIRWAY pressure (wheezing) and PA pressures

37
Q

What are hypersensitivity reactions to Protamine?

A

Uticaria, angioedema, Pulm. HTN, Anaphylactoid reaction, anaphylaxis

38
Q

What may trigger a hypersensitivity reaction?

A

Fish allergy
previous protamine reversal
Protamine containing NPH
Vasectomy

39
Q

How can Protamine be pretreated?

A

Corticosteroid and anithistamine

40
Q

This occurs when pt. recoagulates after protamine admin. usually 8-9hours, or 30min. to 18hours after CPB.

A

Heparin Rebound

41
Q

What are the 3 LMWH discussed?

A
Dalteparin Sodium (Fragmin)
Enoxaparin Sodium (Lovenox)
Tinzaparin Sodium (Innohep)
42
Q

MOA of LMWH?

A

produce anticoagulant effect mainly through inhibition of Factor Xa by antithrombin
-have some Factor IIa inhibition effect

43
Q

Are aPTT and PT sensitive for monitoring LMWH therapy?

A

NO, but you could monitor anti-factor Xa levels

44
Q

What are advantages and uses to using LMWH?

A
  • it is not required monitoring or dosage adjustments
  • prevention of post-op DVT/thromboembolism
  • unstable angina, non-Q wave MI, recurrent DVT, A. fib
45
Q

Can LMWH and/or unfractionated heparin be dosed interchangeably?

A

No

46
Q

What are adverse effects of LMWH?

A

Thrombocytopenia
cant use with patients with HIT
decrease dose in patients with chronic renal insufficiency

47
Q

MOA of Fondaparinux (AriXtra)?

A

Synthetic indirect specific inhibitor of Factor Xa

  • ATIII mediated
  • no effect on Factor IIa
  • No effect on platelet function
48
Q

Advantages of Fondaparinux. . .

A

Fixed dose, once daily SQ administration

-Does not require