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Delta Med - Haematology > Haemostasis and thrombosis > Flashcards

Haemostasis and thrombosis Flashcards

1
Q

What are some of the functions of thrombin?

A 
Platelet activation
Anti-fibronolysis
Conversion of FV, FVIII to FVa, FVIIIa
Cleavage of fibrinogen to fibrin
Inflammation
Protein C activation and anticoagulation
FXI activation
FXIII activation and fibrin stabilisation
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2
Q

Where is tissue factor expressed?

A

On all tissues except for undamaged endothelium.
Can be induced to be expressed on damaged endothelium
Induced expression on leucocytes (monocytes), and fibroblasts - DIC

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3
Q

What are examples of factor inhibitors on mixing studies?

A 
Specific inhibitors on Hx
Non specific:
 - lupus a/c
 - cancer
 - paraprotein
Drugs
 - DTI
 - Heparin
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4
Q

What are causes of MAHA?

A
  • CAPS
  • DIC
  • TTP
  • HUS
  • HELLP
  • HIT
  • Malignant hypertension
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5
Q

What is the leading cause of death in industrial nations?

A

Thromboembolism

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6
Q

What is the rate of post-thrombotic syndrome in TE? Pulmonary hypertension?

A

20-40% for PTS, 5-10% for pulmonary hypertension

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7
Q

What is the recurrence rate of TE?

A

1 year 13%, 10 year +30%

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8
Q

What is the clinical prevalence of TE in cancer populations?

A

up to 20%

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9
Q

How much does death increase in the 1st year following TE in cancer?

A

4 times - (second only to death by cancer itself)

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10
Q

What is the overall risk reduction of DVT and PE in Thromboprophylaxis?

A

60% RRR in DVT

42% RRR in PE

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11
Q

What is the relative reduction of PE in surgical populations on thromboprophylaxis?

A

8 times decrease in PE.

7 lives saved for 100 people treated.

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12
Q

What are bleeding rates in patients on thromboprophylaxis?

A

Approx 0.2-1.5%

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13
Q

What are components of the simplified wells score? (PE)

A 
prior TE
HR >95
recent surgery/immobility/#
Haemoptysis
Active malignancy
Clinical signs of DVT/pain on palpation/oedema
Unlikely alternative diagnosis
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14
Q

In patients with suspected DVT, in which populations is a USS indicated 1st?

A

Likely clinical probability patients should have USS 1st, with low probability patients having d-dimer as 1st line investigation.

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15
Q

What is the mortality rate of PE?

A

20% will die before Dx or within 24 hours.

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16
Q

What PE severity scores can be used?

A

PESI!

Simplified PESI (>=1 point is high risk)

  • Age >80
  • Cancer
  • Heart failure
  • Chronic lung disease
  • SaO2 =110
  • SBP 80 years, critical limb ischaemia
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17
Q

Thrombolysis?

Intent, survival, complications?

A

Does not reduce risk/rate PE or mortality.
Increased risk of ICH
PE - haemodynamic compromise, failing standard therapy
DVT - threatened limb ischaemia, catheter directed.
CVAD - preservation of catheter - alteplase

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18
Q

Outpatient management of PE?

A 
Low risk of death - PESI I or II
No O2 requirement
No narcotic requirement
Nil respiratory distress
Normal BP/HR
No recent bleeding/RFs for bleeding
Normal mental status with understanding of risks and benefits, good support
No concomitant DVT
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19
Q

Benefit of IVC filters?

A

Only as bridge to anticoagulation.
NO BENEFIT compared to anticoagulation with respect to OS at 8 years and at 180 days.

Only use if unable to deliver ANY anticoagulation and there is a below diaphragm DVT

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20
Q

Action of UFH, LMWH, Danaparoid, Fondaparinux

A

All have Anti-Xa activity, however UFH has 1:1 activity also against IIa. 2-4:1 in LMWH, 22:1 in danaparoid, no anti-IIa activity in fondaparinux

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21
Q

Is LMWH superior to UFH in general patients?

A

Yes. Meta-analyses find lower rates of Recurrent VTE, major bleeding and mortality.

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22
Q

Is LMWH safe in patients with ESRD?

A

Yes! JAMA 2015 article found that ther ewas no significant difference in adverse outcomes in patients receiving LMWH for HD

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23
Q

LMWH vs UFH in cancer patients?

A

Superior with respect to mortality, PE, DVT, major bleeding and wound hematoma

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24
Q

What is the renal excretion of LMWH?

A

80-100%

Must monitor anti-Xa levels with GFR 48h) with GFR between 30 and 60.

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25
Q

What enzymatic pathways does rivaroxaban inhibit?

A

CYP3A4 and p-glycoprotein

26
Q

What are important drug reactions with dabigatran?

A

quinidine, amiodarone (potent P-gp inhibitors)

27
Q

What are the mechanisms of actions of DOACs?

A

Dabigatran - direct thrombin inhibitor

Apixaban, rivaroxaban, edoxaban - Xa inhibitors

28
Q

What of the DOACs is most renally excreted?

A

Dabigatran 80%

Apixaban is 25%, Rivarox 33%, Edoxaban 35%

29
Q

What are PBS indications for rivaroxaban?

A

VTE prevention after major orthopedic surgery.
VTE treatment
Stroke prevention in AF

30
Q

What are PBS indications for apixaban?

A

VTE prevention after major orthopedic surgery

Stroke prevention in AF

31
Q

What are PBS indications for dabigatran?

A

VTE prevention following major orthopedic surgery
Stroke prevention in AF

Also shown to be effective as treatment of VTE

32
Q

What two DOACs are inferior wrt safety in primary thromboprophylaxis?

A 
rivaroxaban
apixaban (both compared to enoxaparin)
33
Q

Which DOACs are inferior from a GI bleeding perspective when compared to warfarin in NVAF?

A

dabigatran 110mg/150mg, rivaroxaban

34
Q

In acute DVT, what was the finding of the EINSTEIN study?

A

That rivaroxaban was non-inferior to enoxaparin and VKA.

35
Q

What was the finding of the Amplify study?

A

Apixaban is non-inferior to enoxaparin/VKA in the treatment of acute TE.

WAs superior with respect to major bleeding.

36
Q

What were the findings in DOACs with respect to extended secondary prevention?

A

Dabigatran and rivaroxaban were inferior to placebo, apixaban was non-inferior.

37
Q

What are annual bleeding rates for anticoagulants?

A 
VKA 2-3%/year
Heparins 0-2% (prophylaxis 0.1-0.5%)
NOACs:
rivaroxaban 0.7-6%
apixaban 0.6-2.2%
edoxaban 1.4-2.8%
dabigatran 0.6-4%
38
Q

What are risk factors for bleeding in anticoagulation?

A 
Intensity of a/c
Age
renal function
hepatic function
concomitant drugs
comorbidities 
low body weight
39
Q

What sub-group of DOAC patients has a higher risk of major bleeding in a recent meta-analysis?

A

Patients >=80yo taking 150mg BD of dabigatran.

40
Q

What is a reversal agents for dabigatran, recently approved by the FDA?

A

idarucizumab - a humanised Fab fragment

41
Q

What are strategies in reversing FXa inhibitors?

A
  • activated charcoal is unlikely to be useful
  • HD - highly protein bound, only partial renal clearance
  • PCC is in preference to rFVIIa
42
Q

What are strategies in reversing dabigatran?

A

Can use oral activated charcoal in the first 1-2 hours post ingestion
Target bleeding source
Haemodialysis - low protein binding and renal clearance (30-60% of dose)
PCC
rVIIa

43
Q

What are absolute C/Is to using a DOAC in AF?

A

mechanical valves/valvular AF

CrCL

44
Q

What are minimum durations of anticoagulation in absence of ongoing risk factors?

Distal DVT
Proximal DVT
Pulmonary embolus
CVAD related
Upper limb, non-cvad related
A 
Distal DVT - 3 months
Proximal DVT - 6 months
Pulmonary embolus - 12 months
CVAD related - while in situ + 3 months
Upper limb, non-cvad related 3 months
45
Q

What risk factor has the highest HR for DVt recurrence?

A

increased d-dimer 2.35
male gender 1.56
residual vein thrombus 1.5

46
Q

What are other scores for risk recurrence?

A

HERDOO - D-dimer, BMI, Age >65

DASH - d-dimer elevated, age, male, hormone therapy (negative)

47
Q 
What are ORs for TE in inherited thrombphilias?
FVL heterozygote
PT gene mutation
PC/PS/AT deficiency
MTHFR mutation
A

FVL heterozygote = 4
PT gene mutation = 2
PC/PS/AT deficiency = 10/30/20
MTHFR mutation = 2

48
Q

What should be tested in pt with suspected thrombophilia with a FHx?

A 
APC resistance
Prothrombin mutation
Antiphospholipid Ab
Plasma homocysteine
Factor VIIIc
Antithrombin
Protein C
Protein S
49
Q

What should be tested in pt with suspected non-heritable thrombophilia?

A 
Activated protein C resistance
Prothrombin mutation
Antiphospholipid Ab
Plasma homocysteine
Factor VIIIc
50
Q

Should thrombophilia screening be undertaken in the acute presentation?

A

NO. the results are affected by the thrombosis, and Protein C/S are affected by warfarin therapy, and heparin may lower ATIII levels.

51
Q

When is screening for thrombophilia not recommended?

A

Recent major surgery/trauma/immobilisation
Active malignancy
HITs
Pre-eclampsia at term
UNLESS previous unprovoked VTE or strong FHx of VTE

52
Q

What is the increase in risk of cancer following idiopathic TE?

A

10% of pts with idiopathic ca have occult ca.
OR 1.3-4.4
Strongest assoc with pancreatic, ovarian, hepatic and brain malignancies
increased risk of metastatic cancer at Dx - 40% with occult VTE and cancer Dx within 1 year

53
Q

Is a restricted screening program for cancer preferred to an extended? What forms a restricted screen?

A 
Clinical: Hx, Ex, PR, breast
Labs:
FBC, Film
eLFTs
SPEP
CEA, aFP, PSA, CA125
Radiology: CXR
  • extended screening detects more cancer, but with no real survival benefit
  • PET does have excellent negative predictive value for cancer
54
Q

What are risks of blood transfusion?

A

Predictor of increased mortality
Associated increased hospital and high level acute care LoS (incl ICU)
Increased readmission
Increased risk of infection
Thromboembolism risk (Microvasc/endothelial)
Transfusion related immunomodulation (TRIM)

55
Q

What is the relationship between transfusion and infection rate

A

Dose response relationship exists.

For every 1000 pts considered for transfusion, 26 could be spared risk of infection if restrictive transfusion strategies are used.

56
Q

What thresholds for transfusion are assoc with increased bleeding risk?

A

Plts 1.5 ULN

aPTT - no data

57
Q

When are platelets indicated?

A

Bleeding due to:
Thrombocytopenia
Defective plt function
not usually effective in ITP or immune platelet destruction

58
Q

When is fresh frozen plasma indicated?

A

Correction of bleeding risk where there is multiple factor deficiency - DIC, liver dz, dilutional coagulopathy, TTP

Not to be used where there are specific abnormalities, albumin deficiency, volume expansion

59
Q

What are the contents of cryoprecipitate, and when is it indicated?

A

Concentrated vWF, FVIII, FXIII, fibronectin

Can be used in fibrinogen deficiencies, dysfibrinogenaemia, DIC, vWD

60
Q

What factors are in prothrombin x?

A

Concentrated FII, IX, X and low levels of VII

Contraindicated in thrombosis, DIC, AMI

61
Q

What is DDVAP and what is it used for?

A

synthetic analogue of ADH
increases vWF and FVIII levels.
Enhances haemostasis in patients with platelet function deficits.

62
Q

What is the MoA of tranexamic acid?

A

displaced plasminogen from fibrin and inhibits fibrinolysis

Delta Med - Haematology (3 decks)

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