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Time Completed: 01:07:02

Final Score 54%

98
82

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Pharmacology

Cardiovascular

Question 161 of 180

Unfractionated heparin therapy is monitored using which of the following:

Answer:

Unfractionated heparin is usually given by continuous intravenous infusion for the smoothest control and is the treatment of choice where rapid reversal of anticoagulation may be required (e.g. in surgical patients or late pregnancy). Therapy is monitored by maintaining the activated partial thromboplastin time (APTT) at 1.5 - 2.5 times the upper limit of normal.

The main use of anticoagulants is to prevent thrombus formation or extension of an existing thrombus in the slower-moving venous side of the circulation, where the thrombus consists of a fibrin web enmeshed with platelets and red cells. Anticoagulants are of less use in preventing thrombus formation in arteries, for in faster-flowing vessels thrombi are composed mainly of platelets with little fibrin.

Mechanism of Action

Unfractionated heparin potentiates the activity of antithrombin III, causing inactivation of thrombin. The heparin-antithrombin III complex also inhibits factor Xa and some other factors.

Low molecular weight heparin (LMWH) preparations inhibit only factor Xa.

PT and APTT may both be prolonged but the PT less so.

Contraindications

Heparins are contraindicated:

  • In people with current (or history of) heparin-induced thrombocytopenia
  • In people with acute bacterial endocarditis
  • In people with active major bleeding, and conditions with a high risk of uncontrolled bleeding, including recent haemorrhagic stroke, major trauma, recent brain, spinal cord or eye surgery, haemophilia and thrombocytopenia
  • In people with active gastric or duodenal ulceration

Side Effects

  • Bleeding
  • Heparin-induced thrombocytopenia (immune-mediated effect that usually develops after 5 - 10 days, signs may include a 30% reduction of platelet count, thrombosis, or skin allergy; if HIT is suspected or confirmed, heparin should be discontinued and an alternative anticoagulant given)
  • Hyperkalaemia (due to inhibition of aldosterone secretion; patients with diabetes mellitus, chronic renal failure, acidosis, raised plasma potassium or those taking potassium-sparing drugs seem to be more susceptible)
  • Osteoporosis (risk lower with LMWH)
  • Alopecia
  • Hypersensitivity reactions
  • Injection site reactions

Low Molecular Weight Heparin vs Unfractionated Heparin

Unfractionated heparin (UFH) is usually given by continuous intravenous infusion for the smoothest control and is the treatment of choice where rapid reversal of anticoagulation may be required (e.g. in surgical patients or late pregnancy). Therapy is monitored by maintaining the APTT at 1.5 - 2.5 times the upper limit of normal. Important advantages of UFH compared to LMWHs are that its renal excretion is minimal, it has a relatively short half-life and its effects can be easily monitored by aPTT and rapidly reversed by protamine. The use of UFH may be preferred over LMWHs for treatment indications in patients with severe renal impairment.

Low molecular weight heparin (LMWH) preparations have largely replaced unfractionated heparin.

Advantages of LMWH
Greater ability to inhibit factor Xa directly, interacting less with platelets and so may have a lesser tendency to cause bleeding
Greater bioavailability and longer half-life in plasma making once daily subcutaneous administration possible
More predictable dose response avoiding the need for routine anticoagulant monitoring
Lower associated risk of heparin-induced thrombocytopenia or of osteoporosis

Haemorrhage

Because it has a short duration of action, if haemorrhage occurs it is usually sufficient to withdraw unfractionated or low molecular weight heparin, but if rapid reversal of the effects of the heparin is required, protamine sulfate is a specific antidote (but only partially reverses the effects of low molecular weight heparins).

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  • Biochemistry
  • Blood Gases
  • Haematology
Biochemistry Normal Value
Sodium 135 – 145 mmol/l
Potassium 3.0 – 4.5 mmol/l
Urea 2.5 – 7.5 mmol/l
Glucose 3.5 – 5.0 mmol/l
Creatinine 35 – 135 μmol/l
Alanine Aminotransferase (ALT) 5 – 35 U/l
Gamma-glutamyl Transferase (GGT) < 65 U/l
Alkaline Phosphatase (ALP) 30 – 135 U/l
Aspartate Aminotransferase (AST) < 40 U/l
Total Protein 60 – 80 g/l
Albumin 35 – 50 g/l
Globulin 2.4 – 3.5 g/dl
Amylase < 70 U/l
Total Bilirubin 3 – 17 μmol/l
Calcium 2.1 – 2.5 mmol/l
Chloride 95 – 105 mmol/l
Phosphate 0.8 – 1.4 mmol/l
Haematology Normal Value
Haemoglobin 11.5 – 16.6 g/dl
White Blood Cells 4.0 – 11.0 x 109/l
Platelets 150 – 450 x 109/l
MCV 80 – 96 fl
MCHC 32 – 36 g/dl
Neutrophils 2.0 – 7.5 x 109/l
Lymphocytes 1.5 – 4.0 x 109/l
Monocytes 0.3 – 1.0 x 109/l
Eosinophils 0.1 – 0.5 x 109/l
Basophils < 0.2 x 109/l
Reticulocytes < 2%
Haematocrit 0.35 – 0.49
Red Cell Distribution Width 11 – 15%
Blood Gases Normal Value
pH 7.35 – 7.45
pO2 11 – 14 kPa
pCO2 4.5 – 6.0 kPa
Base Excess -2 – +2 mmol/l
Bicarbonate 24 – 30 mmol/l
Lactate < 2 mmol/l

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