Pharmacology
Cardiovascular
Regarding heparin-induced thrombocytopaenia (HIT), which of the following statements is CORRECT:
Answer:
Heparin induced thrombocytopenia (HIT) is a clinicopathological syndrome that occurs when heparin dependent IgG antibodies bind to heparin/platelet factor 4 complexes to activate platelets and produce a hypercoagulable state. HIT typically develops 5-10 days (range 4-15 days) after heparin is started and can occur with unfractionated heparin, low molecular weight heparin, or, rarely, fondaparinux. Diagnosis requires the combination of a compatible clinical picture and laboratory confirmation of the presence of heparin dependent platelet activating heparin induced thrombocytopenia (HIT) antibodies. Neither discontinuation of heparin alone nor initiation of a vitamin K antagonist alone (for example, warfarin) is sufficient to stop the development of thrombosis in patients with acute HIT. If clinical suspicion for HIT is at least moderate, all sources of heparin must be discontinued and treatment with a non-heparin anticoagulant considered.Heparin
Pharmacology / Cardiovascular
Last Updated: 19th June 2019
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 |
