Recommendation grades (A-C) and levels of evidence (Ia-IV) are defined at the end of the "Major Recommendations" field.
Clinical Presentations and Diagnosis
- All patients who are to receive heparin of any sort should have a platelet count performed on the day of starting treatment. Grade C Level IV.
- For patients who have been exposed to heparin in the last 100 days a baseline platelet count and a platelet count 24 hours after starting heparin should be obtained. Grade C Level IV.
- For all patients receiving unfractionated heparin (UFH), alternate day platelet counts should be performed from days 4 to 14. Grade C Level IV.
- For surgical and medical patients receiving low-molecular-weight heparin (LMWH), platelet counts should be performed every 2–4 days from days 4 to 14. Grade C Level IV.
- Obstetric patients receiving treatment doses of LMWH should have platelet counts performed every 2–4 days from days 4 to 14. Obstetric patients receiving prophylactic LMWH are at low risk and do not need routine platelet monitoring. Grade C Level IV.
- If the platelet count falls by 50% or more and/or the patient develops new thrombosis or skin allergy between days 4 and 14 of heparin administration, heparin-induced thrombocytopenia (HIT) should be considered and a clinical assessment made. Grade C Level IV.
- If the pretest probability of HIT is high, heparin should be stopped and an alternative anticoagulant started in full dosage whilst laboratory tests are performed unless there are significant contraindications. Grade C Level IV.
Laboratory Tests
Platelet Activation Assays, Antigen Assays, Diagnostic Interpretation
- Platelet activation assays using washed platelets have a higher sensitivity than platelet aggregation assays but are technically demanding and their use should be restricted to laboratories experienced in the technique. Grade C Level IV.
- Non-expert laboratories should use an antigen assay of high sensitivity. Only the immunoglobulin G (IgG) class needs to be measured. Useful information is gained by reporting the actual optical density, inhibition by heparin, and the cut-off for a positive test rather than simply reporting the test as positive or negative. Grade B Level III.
- In making a diagnosis of HIT the clinician's estimate of the pretest probability of HIT together with the type of assay used and its quantitative result (enzyme-linked immunosorbent assay [ELISA] only) should be used to determine the post-test probability of HIT. Grade C Level IV.
Treatment
General Principles
- Clinical decisions should be made following consideration of the risks and benefits of treatment with an alternative anticoagulant. Grade C level IV.
- For patients with strongly suspected or confirmed HIT, heparin should be stopped and full-dose anticoagulation with an alternative, such as lepirudin or danaparoid, commenced (in the absence of a significant contraindication). Grade B level III.
- Warfarin should not be used until the platelet count has recovered. When introduced, an alternative anticoagulant must be continued until the International Normalised Ratio (INR) is therapeutic for two consecutive days. Grade C level IV.
- Platelets should not be given for prophylaxis. Grade C level IV.
Lepirudin
- Lepirudin at doses adjusted to achieve an activated partial thromboplastin time (APTT) ratio of 1.5–2.5 reduces the risk of reaching the composite endpoint of limb amputation, death or new thrombosis in patients with HIT and HIT with thrombosis (HITT). Grade B level III.
- The risk of major haemorrhage is directly related to the APTT ratio, lepirudin levels and serum creatinine levels. The patient's renal function needs to be taken into careful consideration before treatment with lepirudin is commenced. Grade B level III.
- Severe anaphylaxis occurs rarely in recipients of lepirudin and is more common in previously exposed patients. Grade C level IV.
Danaparoid
- Danaparoid in a high-dose regimen is equivalent to lepirudin in the treatment of HIT and HITT. Grade B Level III.
- Danaparoid at prophylactic doses is not recommended for the treatment of HIT or HITT. Grade B Level III.
Cardiac Surgery
- Patients with previous HIT who are antibody negative (usually so after >100 days) who require cardiac surgery should receive intra-operative UFH in preference to other anticoagulants that are less validated for this purpose. Pre- and postoperative anticoagulation should be with an anticoagulant other than UFH or LMWH. Grade C level IV.
- Patients with recent or active HIT should have the need for surgery reviewed and delayed until the patient is antibody negative if possible. They should then proceed as above. If deemed appropriate, early surgery should be carried out with an alternative anticoagulant. Grade C level IV.
- The Task Force recommends discussion of these complex cases requiring surgery with an experienced centre. Grade C level IV.
Patient Information and Record Keeping
- The diagnosis must be clearly recorded in the patient's medical record. Grade C, level IV.
Definitions:
Type of Evidence
Ia Evidence obtained from meta-analysis of randomised controlled trials.
Ib Evidence obtained from at least one randomised controlled trial
IIa Evidence obtained from at least one well-designed controlled study without randomisation
IIb Evidence obtained from at least one other well-designed quasi-experimental study
III Evidence obtained from well-designed non-experimental descriptive studies, such as comparative studies, correlation studies and case–control studies
IV Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities
Grade of Recommendations
Grade A (evidence levels Ia, Ib) Requires at least one randomised controlled trial as part of the body of the literature of overall good quality and consistency addressing the specific recommendation
Grade B (evidence levels IIa, IIb, III) Requires availability of well-conducted clinical studies but no randomized clinical trials on the topic of recommendation
Grade C (evidence level IV) Requires evidence from expert committee reports or opinions and/or clinical experience of respected authorities. Indicates absence of directly applicable studies of good quality
