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Can this be HIT as the patient is not now receiving heparin?

In a few cases (3 to 5% of HIT patients) the onset of thrombocytopenia in HIT begins several days after heparin has been stopped(1). These patients with delayed-onset HIT have typically high titers of PF4/heparin reactive antibodies that can cause substantial platelet activation even in the absence of heparin(2).

Delayed HIT should be suspected in any patient who has had heparin discontinued for several days and then presents with an arterial or venous thrombotic event.

1.  Warkentin TE, Greinacher A, Koster A, Lincoff AM. Treatment and prevention of heparin-induced thrombocytopenia: ACCP evidence based clinical practice guidelines (8th Edition). Chest 2008; 133:340-380

2. Warkentin TE, Kelton JG. Delayed onset heparin-induced thrombocytopenia and thrombosis Ann Intern Med 2001; 135:502-6


The platelet count does not seem to be low enough for HIT; what is the definition of thrombocytopenia in HIT?

More than 90% of patients with clinical HIT have a platelet count fall of 50% or more during treatment with heparin (1, 2).  In postoperative patients in particular, a 50% fall in platelet count between days 4 and 14 after surgery is strongly associated with HIT antibodies even without the nadir falling to below 150 x 109 /L.

A median platelet nadir of approximately 60 x 109 /L has been reported in patients with HIT and rarely, in fewer than 5-10% of patients, 20 x109 /L or less (2). This contrasts with ‘typical ‘drug–immune thrombocytopenic purpura for which the median platelet count is 20 x109 /L or less and patients usually develop bleeding.

An important feature of HIT in younger patients is that thrombosis may manifest 1 or a few  days before the platelet count decrease. This occurs in about 25% of patients with HIT and thrombosis (1,3).

1. Warkentin TE, Greinacher A, Koster A, Lincoff AM. Treatment and prevention of heparin-induced thrombocytopenia: ACCP evidence based clinical practice guidelines (8th Edition). Chest 2008; 133:340-380

2.Warkentin TE. Clinical Picture of HIT. In: Warkentin TE and Greinacher A, eds. Heparin-induced thrombocytopenia. 4th ed. New York, Informa Healthcare, 2007; 21-66

3. Greinacher A. et al. Clinical features of heparin-induced thrombocytopenia including risk factors for thrombosis. Thromb Haemost 2005; 94:132-135 


Should we wait for laboratory test results to come back to confirm HIT before treating ?

The decision to treat should not wait for laboratory confirmation because of the time delay in obtaining results. This is because there is a high risk of thrombosis in HIT despite discontinuation of heparin therapy. Among patients with HIT associated thrombocytopenia, the initial rate of thrombosis is about 5-10% per day over the first 1-2 days after stopping heparin and the cumulative 30 day risk is about 50% (1).

The initial diagnosis of HIT should be made on clinical grounds, based on a decrease in platelet counts between 5 and 14 days after heparin exposure, excluding other possible causes. The 4T’s provides a simple scoring system to estimate the probability of HIT (2).

1.Warkentin TE. Clinical Picture of HIT. In: Warkentin TE and Greinacher A, eds. Heparin-induced thrombocytopenia. 4th ed. New York, Informa Healthcare, 2007; 21-66

2.Lo GK, Juhl D, Warkentin TE et al. Evaluation of pretest clinical score (4T’s) for the diagnosis of heparin–induced thrombocytopenia in two clinical settings. J Thromb Haemost 2006; 4:759-65


Is just stopping heparin enough?

Stopping heparin is the first step but just discontinuing heparin does not eliminate the danger of new thrombosis in HIT. A number of studies have shown that there is a substantial risk of new thrombosis in patients who present with isolated HIT (HIT without thrombosis) after heparin was discontinued. The initial rate of thrombosis is about 5-10% per day over the first 1-2 days and the cumulative 30 day risk is about 50% (1).


1.Warkentin TE. Clinical Picture of HIT. In: Warkentin TE and Greinacher A, eds. Heparin-induced thrombocytopenia. 4th ed. New York, Informa Healthcare, 2007; 21-66


Can we use low molecular weight heparins in HIT?

Low molecular weight heparins (LMWH) should not be used in HIT. Although LMWH are less likely to cause HIT and HIT antibody formation, LMWH show cross-reactivity with HIT antibodies in functional assays for HIT. In the past HIT has been treated with LMWH but persistent thrombocytopenia and disastrous complications were reported.

 Warkentin TE, Greinacher A, Koster A, Lincoff AM. Treatment and prevention of heparin-induced thrombocytopenia: ACCP evidence based clinical practice guidelines (8th Edition). Chest 2008; 133:340-380



Can we just start warfarin/phenprocoumon ?

Vitamin K antagonists such as warfarin and phenprocoumon can exacerbate the prothombotic state in HIT causing thombosis to progress in the microvasculature and coumarin-induced venous limb gangrene.  This is because VKA treatment produces a transient but marked reduction in levels of the natural anticoagulant Protein C, while thrombin generation remains high during HIT.

It is recommended that (1):

  • VKA therapy is not used  in patients with suspected or confirmed HIT until after the platelet count has substantially recovered (e.g. usually to at least 150 x 109 /L)
  • the VKA should be administered only during overlapping alternative anticoagulation (minimum 5-day overlap)
  • the VKA  is begun with low, maintenance doses (maximum, 5 mg warfarin  and 6 mg of phenprocoumon)
  • the alternative anticoagulant is not  stopped until the platelet count has reached a stable plateau and the INR is within the target therapeutic range for at least 2 days.

For patients receiving VKA’s at the time of a diagnosis of HIT the use of vitamin K (e.g. 10 mg oral or 5-10 mg IV) is recommended.

1.  Warkentin TE, Greinacher A, Koster A, Lincoff AM. Treatment and prevention of heparin-induced thrombocytopenia: ACCP evidence based clinical practice guidelines (8th Edition). Chest 2008; 133:340-380


Can I give heparin to a patient with a remote history of HIT?

HIT antibodies to heparin are not usually detected 3 months after an episode of HIT. However, there are very few reports of patients with previously documented HIT (after 3 months) who have been re-exposed to heparin. As there are acceptable alternative anticoagulants, it is recommended that heparin should not be used for antithrombotic prophylaxis or therapy in a patient with a previous history of HIT, except under special circumstances (e.g. cardiac or vascular surgery).

Greinacher A and Warkentin TE. Treatment of HIT: an overview. In: Warkentin TE and Greinacher A, eds. Heparin-induced thrombocytopenia. 4th ed. New York, Informa Healthcare, 2007; 283-317


Can I use heparin in surgery in patients with a remote history of HIT?

In patients with a history of HIT and no HIT antibodies, it is feasible to give heparin during heart or vascular surgery, provided that heparin use is restricted to the surgical procedure itself. Preoperative and postoperative antithrombotic anticoagulation should be carried out with an alternative non-heparin anticoagulant.

Warkentin TE, Greinacher A, Koster A, Lincoff AM. Treatment and prevention of heparin-induced thrombocytopenia: ACCP evidence based clinical practice guidelines (8th Edition). Chest 2008; 133:340-380


My patient has HIT with thrombocytopenia and no thrombus, should I use a prophylactic/low dose?

In patients with strongly suspected or confirmed HIT, even in the absence of a thrombus (isolated HIT), it is recommended that an alternative non-heparin anticoagulant is used in therapeutic doses (1). Therapeutic doses should be used because of the high thrombotic risk associated with HIT. A thrombotic event rate of about 50% has been reported over 30 days in patients with isolated HIT.  Low-dose (i.e. doses used in prophylaxis) danaparoid was associated with a high failure rate when administered for isolated HIT (2).

The high event rate suggests that many patients with isolated HIT may have sub-clinical deep vein thrombosis (DVT). It is also recommended that patients suspected to have acute HIT should undergo imaging studies for lower limb DVT (1).

1. Warkentin TE, Greinacher A, Koster A, Lincoff AM. Treatment and prevention of heparin-induced thrombocytopenia: ACCP evidence based clinical practice guidelines (8th Edition). Chest 2008; 133:340-380

2. Farner et al. A comparison of danaparoid and lepirudin in heparin-induced thrombocytopenia. Thromb Haemost 2001; 85:950-7


There is only a low probability that my patient has HIT, what should I do while waiting for laboratory results?

If HIT is unlikely (e.g. a 4T’s score of ?3) and there is no other reason for therapeutic dose anticoagulation; it is suggested that heparin could be continued or alternative anticoagulants used in low doses, until the results of laboratory tests are known. The risk of bleeding from using another anticoagulant should be balanced against the low probability of thrombosis in these patients.

Greinacher A and Warkentin TE. Treatment of HIT: an overview. In: Warkentin TE and Greinacher A, eds. Heparin-induced thrombocytopenia. 4th ed. New York, Informa Healthcare, 2007; 283-317


I cannot rule out HIT, but there are other more likely reasons for thrombocytopenia, what should I do while waiting for test results?

If there are other more likely reasons for thrombocytopenia than HIT, the patient may be at an increased bleeding risk. Therefore, if the patient has an intermediate risk of HIT (e.g. 4T’s score <4) and does not require therapeutic-dose anticoagulation for other reasons; it is suggested that low (i.e. as recommended for prophylaxis) doses of danaparoid or low initial doses of DTI’s (adjusted according to aPTT) are considered. 

However, if HIT is strongly suspected then heparin should be stopped and an alternative anticoagulant used at therapeutic doses.

Greinacher A and Warkentin TE. Treatment of HIT: an overview. In: Warkentin TE and Greinacher A, eds. Heparin-induced thrombocytopenia. 4th ed. New York, Informa Healthcare, 2007; 283-317


Can I use fondaparinux?

There are a few published case reports which suggest that fondaparinux may be an option in HIT. However, fondaparinux is not approved for use in HIT and the available evidence is too limited to draw definite conclusions about its safety and efficiency in this patient population(1). Three cases of HIT have been reported as associated with fondaparinux (2,3,4). HIT is an iatrogenic induced adverse effect. It is becoming an increasing medicolegal issue. Therefore, it may be prudent to obtain informed consent and to document the reasons for preference of the respective drug, if a non-approved alternative anticoagulant is used in HIT.

1. Greinacher A and Warkentin TE. Treatment of HIT: an overview. In: Warkentin TE and Greinacher A, eds. Heparin-induced thrombocytopenia. 4th ed. New York, Informa Healthcare, 2007; 283-317

2. Warkentin TE, Maurer BT, Aster RH. Heparin-induced thrombocytopenia associated with fondaparinux [letter]. N Engl J Med 2007; 356(25):2653-2655

3. Rota E, Bazzan M, Fantino G. Fondaparinux-related thrombocytopenia in a previous low-molecular weight heparin(LMWH)-induced heparin-induced thrombocytopenia. Thromb Haemost 2008; 99: 779-781.

4. Warkentin TE, Lim W. Can heparin-induced thrombocytopenia be associated with fondaparinux use? Reply to a rebuttal [Letter to the editor]. J Thromb Haemost 2008; 6(7): 1243-1246


What are the options in haemodialysis?

An alternative anticoagulant is required for haemodialysis in patients with HIT and all forms of heparin must be stopped.  Argatroban, danaparoid and lepirudin have been used  in renal replacement therapy but there are no large scale prospective trials. Both lepirudin and danaparoid have a long half life in severe renal impairment. The predominantly hepatic elimination of argatroban may favour its use in chronic renal failure.

Selleng K, Warkentin TE. Greinacher A.  Heparin-induced thrombocytopenia in intensive care patients. Crit Care Med 2007; 35(4):165-76


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