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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
What enzymatic pathways does rivaroxaban inhibit?
CYP3A4 and p-glycoprotein
26
What are important drug reactions with dabigatran?
quinidine, amiodarone (potent P-gp inhibitors)
27
What are the mechanisms of actions of DOACs?
Dabigatran - direct thrombin inhibitor | Apixaban, rivaroxaban, edoxaban - Xa inhibitors
28
What of the DOACs is most renally excreted?
Dabigatran 80% Apixaban is 25%, Rivarox 33%, Edoxaban 35%
29
What are PBS indications for rivaroxaban?
VTE prevention after major orthopedic surgery. VTE treatment Stroke prevention in AF
30
What are PBS indications for apixaban?
VTE prevention after major orthopedic surgery | Stroke prevention in AF
31
What are PBS indications for dabigatran?
VTE prevention following major orthopedic surgery Stroke prevention in AF Also shown to be effective as treatment of VTE
32
What two DOACs are inferior wrt safety in primary thromboprophylaxis?
``` rivaroxaban apixaban (both compared to enoxaparin) ```
33
Which DOACs are inferior from a GI bleeding perspective when compared to warfarin in NVAF?
dabigatran 110mg/150mg, rivaroxaban
34
In acute DVT, what was the finding of the EINSTEIN study?
That rivaroxaban was non-inferior to enoxaparin and VKA.
35
What was the finding of the Amplify study?
Apixaban is non-inferior to enoxaparin/VKA in the treatment of acute TE. WAs superior with respect to major bleeding.
36
What were the findings in DOACs with respect to extended secondary prevention?
Dabigatran and rivaroxaban were inferior to placebo, apixaban was non-inferior.
37
What are annual bleeding rates for anticoagulants?
``` 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
What are risk factors for bleeding in anticoagulation?
``` Intensity of a/c Age renal function hepatic function concomitant drugs comorbidities low body weight ```
39
What sub-group of DOAC patients has a higher risk of major bleeding in a recent meta-analysis?
Patients >=80yo taking 150mg BD of dabigatran.
40
What is a reversal agents for dabigatran, recently approved by the FDA?
idarucizumab - a humanised Fab fragment
41
What are strategies in reversing FXa inhibitors?
- activated charcoal is unlikely to be useful - HD - highly protein bound, only partial renal clearance - PCC is in preference to rFVIIa
42
What are strategies in reversing dabigatran?
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
What are absolute C/Is to using a DOAC in AF?
mechanical valves/valvular AF | CrCL
44
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 ```
``` 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
What risk factor has the highest HR for DVt recurrence?
increased d-dimer 2.35 male gender 1.56 residual vein thrombus 1.5
46
What are other scores for risk recurrence?
HERDOO - D-dimer, BMI, Age >65 | DASH - d-dimer elevated, age, male, hormone therapy (negative)
47
``` What are ORs for TE in inherited thrombphilias? FVL heterozygote PT gene mutation PC/PS/AT deficiency MTHFR mutation ```
FVL heterozygote = 4 PT gene mutation = 2 PC/PS/AT deficiency = 10/30/20 MTHFR mutation = 2
48
What should be tested in pt with suspected thrombophilia with a FHx?
``` APC resistance Prothrombin mutation Antiphospholipid Ab Plasma homocysteine Factor VIIIc Antithrombin Protein C Protein S ```
49
What should be tested in pt with suspected non-heritable thrombophilia?
``` Activated protein C resistance Prothrombin mutation Antiphospholipid Ab Plasma homocysteine Factor VIIIc ```
50
Should thrombophilia screening be undertaken in the acute presentation?
NO. the results are affected by the thrombosis, and Protein C/S are affected by warfarin therapy, and heparin may lower ATIII levels.
51
When is screening for thrombophilia not recommended?
Recent major surgery/trauma/immobilisation Active malignancy HITs Pre-eclampsia at term UNLESS previous unprovoked VTE or strong FHx of VTE
52
What is the increase in risk of cancer following idiopathic TE?
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
Is a restricted screening program for cancer preferred to an extended? What forms a restricted screen?
``` 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
What are risks of blood transfusion?
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
What is the relationship between transfusion and infection rate
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
What thresholds for transfusion are assoc with increased bleeding risk?
Plts 1.5 ULN | aPTT - no data
57
When are platelets indicated?
Bleeding due to: Thrombocytopenia Defective plt function not usually effective in ITP or immune platelet destruction
58
When is fresh frozen plasma indicated?
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
What are the contents of cryoprecipitate, and when is it indicated?
Concentrated vWF, FVIII, FXIII, fibronectin Can be used in fibrinogen deficiencies, dysfibrinogenaemia, DIC, vWD
60
What factors are in prothrombin x?
Concentrated FII, IX, X and low levels of VII Contraindicated in thrombosis, DIC, AMI
61
What is DDVAP and what is it used for?
synthetic analogue of ADH increases vWF and FVIII levels. Enhances haemostasis in patients with platelet function deficits.
62
What is the MoA of tranexamic acid?
displaced plasminogen from fibrin and inhibits fibrinolysis

Delta Med - Haematology (3 decks)

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