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Flashcards in Medical therapy Deck (136):
1

What is the maximum dose infusion of tPA?

2 mg/hr

2

What is the maximum total dose of tPa?

100 mg

3

What level of fibrinogen do you stop tPA?

100 mg/dL or < 1 g/L

4

What hematologic investigations are required for: Patients who have no bleeding history and will undergo minor procedures, such as lipoma excision.

None

5

What hematologic investigations are required for: Patients who have no previous bleeding history but will undergo a major operation.

aPTT and platelet count

6

What hematologic investigations are required for: Patients whose bleeding history raises concern for defective hemostasis and those whose procedure might impair hemo- stasis (e.g., cardiac or neurosurgical interventions).

1) How well will patient form platelet plug? platelet count

2) How effective is coags? PT and aPTT 

3) Size and stability of fibrin clot? Factor 8 deficiency, fibrinolysis screening

7

What hematologic investigations are required for: A history or physical findings highly suggestive of abnormal hemostasis, and the surgical procedure is not a factor.

1) How well will patient form platelet plug? platelet count

2) How effective is coags? PT and aPTT 

3) Size and stability of fibrin clot? Factor 13 deficiency, fibrinolysis screening

4) vWD or qualitiative platelet disorder? Bleeding time after 600 mg ASA

5) Factor 8 and 9 levels

6) Dysfibrogenemia? Thrombin time (TT)

8

Which factors does PT measure?

Extrinsic pathway of clotting: 2, 5, 7, 9, 10, protein c&s, tissue factor, fibrinogen

End point is time required in seconds for a fibrin clot to form

9

What would cause an abnormal PT?

consumptive coagulopathy, warfarin, vit k deficiency, liver disease

10

Which factors does activated partial thrombplastin time (aPTT) measure?

Intrinsic pathway and final common pathway -

All factors except factor 7

11

What blood test do you use to monitor warfarin therapy?

PT/INR

12

What blood test do you use to monitor heparin therapy?

aPTT

13

What would cause an abnormal aPTT?

Consumptive coagulopathy, heparin, lupus anticoagulants

14

What factor does thrombin time (TT) measure?

Fibrinogen (functional)

15

What test do you use to monitor fibrinolysis?

thrombin time (TT)

16

Which variables does activated clotting time measure?

Global clotting function

17

What blood test do you use to monitor intra-op heparin therapy

ACT

18

What factors/variables are measured by bleeding time (BT)?

Platelet number and function

19

What would cause abnormal bleeding time (BT)?

abnormal platelet function, antiplt drugs, thrombocytopenia, uremia, von willebrand disease

20

What variable does thromboelastography measure?

clotting kinetics

21

What blood test is used for monitoring during or after cardiopulmonary bypass?

thromboelastography

22

What variable does fibrin degradation products (FDPs) measure?

Fibrinolysis

23

What does euglobulin lysis time (ELT) measure?

Fibrinolysis - e.g. diagnosing DIC

24

What blood test would help with detecting hemophilia A and B?

aPTT

25

What does ROTEM measure?

like thromboelestography, a point of care testing which measures clotting kinetics. used for directing blood product administration in bleeding trauma, post-partum hemorrhage etc. 

26

Which blood test can help you differentiate DIC from primary fibrinolytic state? 

ELT Euglobulin lysis time (time it takes to lyse a clot). Diagnostic of primary fibronolyis if shortened ELT in patients without thrombcytopenia or schistocytosis

27

What is the most common inherited bleeding disorder?

von willebrand disease

28

What does von willebrand factor do?

Binds to both platelets and endothelial components to build an adhesive bridge for primary hemostasis. also acts as a carrier protein for factor 8

29

What are the 3 types of von willebrand disease?

1 - Autosomal dominant, minimal bleeding

2 - Autosomal but varied, variable bleeding

3 - Autosomal recessive, severe bleeding

30

What type of von willebrand disease have the most severe bleeding?

autosomal recessive

31

What are the 4 types of type 2 von willebrand disease?

2A - loss of high molecular weight multimers => decreased plt function

2B - increased affinity for GP Ib

2M - Reduced binding of GP Ib despite having large vWF multimers

2N - altered factor 8 binding site therefore rapid clearance of 8

32

What should type 1 vWD patients be treated with perioperatively if they have mild to moderate bleeding?

avoid NSAIDS. DDAVP.

33

What should patients with type 3 vWD be treated with?

For serious bleeding or major surgery - replacement therapy - vWF, factor 8-vWF concentrates or cryoprecipitate (goal to keep activity of factor 8/vWF between 50-100% for 3-10 days)

34

What are 4 types of giant platelet disorders?

1 - Structural defects e.g. Bernard Soulier syndrome

2. With abnormal neurtrophils e.g. May-Hegglin

3. With systemic manifestations - hereditary macrothrombocytopenia with hearing loss

4. With no specific abnormalities e.g. Mediterranean macrothrombocytopenia 

35

How do you treat patients with giant platelet disorders?

Education to avoid activities with minor trauma. Platelet transfusion os significant hemorrhage. 

36

What is Glanzmann's thrombasthenia?

An autosomal recessive disease which causes defect in GP 2b 3a which renders platelets unable to aggregate. 

37

What does GP 2b 3a do? 

Allows platelets aggregate and bind to soluble proteins and vWF

38

How do you treat patients with Glanzmann's thrombasthenia who bleed significantly?

Platelet transfusion

39

What are the 2 types platelet granule deficiencies associated with storage pool disorders?

Alpha granules which contain: vWF, fibrinogen, platelet derived growth factor, thrombospondin)

Dense granules which release: ADP and serotonin 

40

What is gray platelet syndrome?

Alpha granule storage disorder. Typically minimal mucosal bleeding. DDAVP given periprocedurally and platelet transfusions. 

41

What factors are deficient in patients with hemophilia A?

Factor 8

42

What factors are deficient in patients with hemophilia B?

Factor 9

43

What factors are deficient in patients with hemophilia C?

Factor 11 (uncommon)

44

Which factor is protected from premature degradation by vWF?

Factor 8

45

How can you clinically distinguish the difference between hemophilia A and B?

Clinically indistinguishable

46

What stage of hemostasis is defective in hemophilia bleeding?

Secondary hemostasis - a normal platelet plug forms but stabilization of plug by fibrin is defective because inadequate thrombin

47

What is the hallmark of severe hemophilia?

Spontaneous bleeding into joints and muscles 

48

How can you raise factor concentrations in patients with mild hemophilia A?

DDAVP

49

Prior to elective surgery, what level of factor 8 is required in hemophilia patients?

Over 80%. Factor 8 concentrations can be given. 

50

What causes acquired platelet dysfunction (7):?

1- uremia

2 - liver disease

3 - cardiopulmonary bypass

4 - hematologic malignancy

5- thrombotic thrombocytopenia purpura

6 - immune thrombocytopenic purpura

7 - hypersplenism

51

How does liver disease result in thrombocytopenia?

Portal hypertension, splenic sequestration and decreased thrombopoietin production 

52

How can you treat actively bleeding uremic patients or those undergoing major surgery?

1 - Correct anemia to hematocrit 25-30% to improve platelet aggregation and adheshion. 

2- DDAVP to enhance release of vWF

3 - Conjugated estrogen - mechanism unknown.

4 - Dialysis for uremic complications

 

53

What are vitamin K dependent coagulation factors?

10, 9, 7, 2 (1972) protein C&S

54

How do you treat bleeding in patients with vitamin K deficiency/on warfarin? 

Treat with vitamin K or FFP. 

55

When reversing warfarin with vitamin K - how long does it take to take effect? How long does it last?

At least 6 h to take effect but more durable reversal than FFP which only lasts 6 h

56

When reversing warfarin with FFP - how long does it take to take effect? How long does it last?

Immediate, lasts 6 h

57

DIC is primarily due to the uncontrolled production of what?

Thrombin - leading to intravascular fibrin deposition and thrombosis of the microvasculature > end organ damage

58

In DIC what causes the coagulopathy?

Thrombosis of the microvasculature leading to end organ damage, initiates systemic tPA release which induces thrombolysis and consumptive coagulopathy

59

What are the most common precipitants of DIC?

Sepsis, malignancy, trauma, amniotic fluid embolism, placental abruption

60

What are the clinical symptoms of the first stage of DIC?

Asymptomatic - compensated activation of hemostatic system

61

What happens to the lab values in the 1st phase of DIC?

1 - PT normal

2 - aPTT normal

3 - TT normal

4 - Platelet count normal

5 - Thrombin antithrombin complex elevated

6 - Prothrombin fragmin elevated

7 - Fibrinogen normal

8 - FDP normal

62

What happens to the lab values in the 2nd phase of DIC?

1 - PT elevated

2 - aPTT elevated

3 - TT elevated

4 - Platelet count decreased

5 - Thrombin antithrombin complex elevated

6 - Prothrombin fragmin elevated

7 - Fibrinogen decreased

8 - FDP elevated

63

What are the clinical features of 2nd phase of DIC?

Bleeding from injuries/venipuncture, renal/hepatic/pulmonary function impaired

64

What happens to the lab values in the 3rd phase of DIC?

1 - PT very elevated

2 - aPTT very elevated

3 - TT very elevated

4 - Platelet count very decreased

5 - Thrombin antithrombin complex elevated

6 - Prothrombin fragmin elevated

7 - Fibrinogen very decreased

8 - FDP very elevated

65

What are the clinical features of 3rd phase of DIC?

Ecchymoses, multiorgan failure

66

What is the overriding goal in treating DIC?

Correcting precipitating disease

67

What is the goal target for resuscitating DIC?

Often have to give factors and platelets. Goal Fibrinogen > 100 mg/dL

68

What can cause a primary hyperfibronolytic state?

Malignancy, liver failure, trauma, congenital deficiency of fibrinolysis inhibitors.

Very difficult to discern from secondary fibrinolysis (DIC) - requires Euglobulin lysis time (ELT)

69

What is the treatment for primary fibrinolysis?

Transexamic acid (and aminocaproic acid). These are competitive inhibitors for the conversion of plasminogen to plasmin. Often factor 5 and 8 also given. 

70

How does heparin work?

Binds to and activates antithrombin preventing clot formation and propgation. Antithrombin accelerates ability to inactivate 2 (thrombin), 10a, and 9a

71

What does a d-dimer measure?

Product of fibrin proteolysis by plasmin - indicates that fibrinolysis happening

72

What other than DVT can cause elevated d-dimer?

Surgery, trauma, pregnancy, malignancy, thrombotic disorders

73

What are 5 duplex findings of a DVT?

Incompressible vein, absense of flow in vein, absent flow augmentation with distal compression, vein diameter increased, increased echogenicity

74

What is the sensitivity of utrasound to identify asymptomatic calf DVTs? 

Only 40%, can't rule out based on ultrasound alone. Wells criteria increases predictive value. 

75

What are 9 elements of the Wells score for DVT?

1 - previous DVT

2 - active cancer

3 - entire leg swollen

4 - tenderness along deep venous territory

5 - collateral veins (not varicose)

6 - pitting edema isolated to affected leg

7 - paralysis/paresis/immobilization

8 - major surgery/bed bound x 3 or more days

9 - calf swelling at least 3 cm larger than other side

76

When do you use d-dimers in DVT workup?

Clinically likely but venous duplex shows no DVT

or clinically unlikely

77

What age of thrombus is thrombolysis effective?

< 10 days, afterwards thrombus is adherent to walls and organized

78

How frequently do DVTs recurr in 1st year?

15%

79

Should you anticoagulate calf DVTs?

Controversial - 2016 chest guidelines state 3 months of anticoagulation

80

How should you treat femoropopliteal DVT?

Usually anticoagulation alone. Sometimes thrombus removal required if clot in the popliteal trifurcation because blocks outflow from entire calf and can have more morbidity. 

81

How should you treat iliofemoral DVT?

Endo/open recanalization. Anticoagulation rarely works alone and 30% will have venous claudication/ulceration

82

Why does unfractionated heparin have to be monitored?

Nonspecific binding (plasma proteins, platelet factor 4, macrophages, endothelial cells) therefore unpredictible pharmacokinetics and narrow therapeutic window

83

What are 5 drawbacks of unfractionated heparin?

1 - need for hospitalization

2 - frequent blood draws

3 - difficulty promptly reaching therapeutic range

4 - potential for HITT

5 - variable response

84

What are 5 advantages of LMWH compared with UFH?

1 - longer half life (3-5h)

2 - more consistent response/no monitoring

3 - less major bleeding

4 - lower mortality

5 - better bioavailability

 

85

How should you treate acute VTE in cancer patients?

2016 chest guidelines suggest LMWH or DOAC over vitamin K antagonists because studies shows higher failure rate of VKA

86

Which 2 drugs have FDA approval to treat HIT?

Direct thrombin inhibitors - argatroban and bivalrudin

87

Why are vitamin K antagonists procoagulant in first 3 days?

Inhibits coagulation factors 10, 9 ,7, 2 but also inhibits natural anticoagulants protein C & S. Protein C & S have much shorter half life so inhibition of these anticoagulants initially make patients prothrombotic.

88

How long do you need to overlap heparin and warfarin?

5 days

89

Name 4 direct acting oral anticoagulants (DOAC) and what they inhibit

1 - Rivaroxaban - Xa

2 - Apixaban - Xa

3 - Edoxaban - Xa

4 - Dabigatran - Thrombin

90

What did the EINSTEIN trial show?

rivaroxaban noninferior to warfarin

91

Which trial showed Apixaban non inferior to warfarin?

Amplify

92

Do DOACs have less major bleeding compared with VKA?

Rivaroxaban - no difference EINSTEIN

Apixaban (amplify), edoxaban (hokusai), dabigatran (recover) has less bleeding

93

What agent reverses dabigatran?

Idaricuzumab

94

How long does idaricuzumab take to reverse dabigatran? How long does it last?

Immediate, 24 h

95

Should you use compression stockings to prevent post thrombotic syndrome?

Chest guidelines 2016 no longer recommend compression stockings, no benefit in SOX trial. But still may be of some use for symptom releif. 

96

How do you know whether to continue anticoagulation for DVT after 3 months?

D-Dimer elevation (PROLONG study). Those with d-dimer elevation and no continuation of anticoagulation had higher VTE recurrence rate. 

97

Which trials showed the benefit of adding ASA to anticoagulation for decreasing long term VTE recurrence? 

WARFASA, ASPIRE, INSPIRE

98

What did AMPLIFY-EXT show?

Addition of low dose apixaban after 6 - 12 months of therapeutic anticoagualtion can reduce recurrence of VTE without significantly increasing bleeding risk (NNT 14 to prevent 1 recurrent VTE)

99

What is the half life of heparin IV and SC?

IV - 1.5 h, SC - 8h

100

Why does warfarin induced skin necrosis occur?

Initial prothrombotic state (inhibition of natural anticoagulants protein C & S) cause small vessel thrombosis of the skin

101

What are 2 disadvantages of DOACs compared with warfarin?

Not easily reversed, no easy access lab test to evaluate therapeutic efficacy

102

How do you manage life threatening bleeding in patient on DOACs?

FFP/cryo wont work. Transfuse blood and PCC (prothrombin concentration complex e.g. octaplex) and recombinant factor 7a

103

When can you hold plavix in patients who underwent bare metal coronary stenting? DES?

6 months for BMS, 1 year for DES

104

How does apiximab work?

GP 2a 3b inhibition -> inhibits platelet aggregation

 

105

What percentage of patients show inadequate platelet inhibition with clopidogrel?

30%

106

How do thrombolytic agents work?

All activate plasminogen, which directly or indirectly convert plasminogen to plasmin then plasmin degrades a number of factors including fibrinogen, fibrin, prothrombin, 5 7 

107

Acidosis can result in coagulopathy. What is a strategy to prevent this effect in reperfusion injury?

Pre-emptive resp and metabolic alkalosis prior to clamp removal

108

What are 6 classes of causes for coaulopathy?

1- inherited coagulopathies

2 - acquired coagulopathies

3 - drug induced

4 - hypothermia

5 - acidosis

6 - dilutional

109

How do you prevent dilutional coagulopathies when resuscitating major bleeding?

Massive transfusions of pRBC need adequate FFP ratio

 

110

Which infusion solution has recognized anticoagulation and antiplatelet properties?

Hypertonic saline

111

What are 4 indications for transfusing pRBC?

American Society of Anesthesiologists - no longer based on Hgb alone. 

1 - Symptomatic anemia,

2- hgb < 60 in healthy patients

3- massive hemorrhage

4-decreased oxygen carrying capacity

112

How much should your platelets go up after transfusing a unit?

30 - 60k uL

113

What are 2 indications to transfuse platelets?

< 10k, or bleeding patient < 50k

114

What does FFP contain?

All clotting factors, esp 10 9 7 2 protein C/S and antithrombin 3

115

What are 5 indications for transfusing FFP?

1 - warfarin related bleeding

2 - massive transfusion 

3 - thrombotic thrombocyotepenic purpura

4 - coag factor deficiencies

5 - anti thrombin 3 deficiency

116

What does cryoprecipitate contain?

Fibrinogen, factors 5, 8, 13, vWF

117

What is are 2 indications to transfuse cryoprecipitate?

1 - Hypofibrinogenemia (consumptive coagulopathy, primary fibrinolysis, therapeutic thrombolysis)

2 - Massive hemorrhage

118

What does DDAVP do?

Desmopressin is an arginine vasopressin analogue that stimulates the release of vwF from the vascular endothelium. 

119

What are 2 indications for DDAVP?

Uremic platelet dysfunction, some von Willebrand diseases

120

What is protamine?

Derived from salmon sperm, protamine reverses heparin

121

What dose of protamine do you give to reverse heparin?

1 mg per 100 units of heparin

122

When do you transfuse factor 7a

Hemophelia. Off label use - massive hemorrhage, ICH, trauma, cardiac surgery

No evidence for these indications and increased thromboembolic events and cost

123

When do you use transexamic acid/aminocaproic acid?

Primary fibrinolysis. 

Surgical patients with high bleeding risk.

2011 cochrane review shows it decreases periop blood loss/allogenic transfusion.

124

What are chitosans?

Deacetylated form of chitin - gauze bandage which promotes rapid hemostatic clot formation

125

What is mineral zeolite?

Absorbs water, thus concentrating clotting factors and platelets. Also may activate factor 12. (Caution - exothermic!) 

126

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136

How long do you hold ASA and plavix before a surgery?

Plavix - 5 days. Typically don't need to hold ASA