Citrasate - Heparin-Induced Thrombocytopenia (HIT) Citrasate HIT

How Significant is Your Heparin Problem? (Print PDF)

Heparin-induced Thrombocytopenia (HIT) occurs in 3% of patients who receive therapeutic intravenous unfractionated heparin and 0.5% - 1% of patients who receive lower doses (subcutaneous or flushes), low- molecular-weight heparin, or even the tiny amounts that leach from heparin-coated catheters. (1-3). HIT can present 5 to 12 days after heparin exposure, with or without arterial or venous thromboemboli. Delayed recognition and treatment of HIT can contribute to poor patient outcomes (4).
Symptoms of HIT include:


Delayed-onset HIT should be a primary diagnostic consideration whenever a recently hospitalized patient presents with thromboembolism. Physicians should be aware that even a modestly low platelet count on representation could be an essential clue to underlying HIT. In such cases, physicians could initiate early alternative anticoagulant therapy, instead of thrombotic diathesis (4). A serologic test for Heparin-induced antibodies and regular monitoring of platelet counts can determine HIT. ONCE HIT IS SUSPECTED, ALL HEPARIN PRODUCTS SHOULD BE DISCONTINUED, WHICH INCLUDE HEPARIN ON HEMODIALYSIS AS WELL AS FOR CATHETER FLUSH.

Alternatives to Heparin include:


The above alternatives to Heparin are expensive, have side effects and are not well proven as good alternatives. Alternatives in hemodialysis include Citrasate® dialysis concentrate and dialyzers that reduce the need for heparin (i.e. REXEED® dialyzers by Asahi Medical). For additional information on these products, call Dial Medical Customer Service at 800-346-2080.

References:
1. Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med. 1995;332:1330-5. [PMID: 7715641]
2. Rice L, Huffman DM, Levine ML, Udden MM, Waddell CC, Luper WE. Heparin-induced thrombocytopenia/thrombosis syndrome: clinical manifestation and insights (Astract). Blood. 1986;68(Suppl 1):339a.
3. Laster J, Silver D. Heparin-coated catheters and heparin-induced thrombocytopenia . J Vasc Surg. 1988;7:667-72. [PMID: 3367431]
4. Rice L, Attisha WK, Drexler A, Francis, JL. Delayed-onset heparin-induced thrombocytopenia. Ann Intern Med. 2002;136;210-215
5. Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med. 1996;101:502-07. [PMID: 8948273]

Treating Hemodialysis Patients with Heparin-Induced Thrombocytopenia (HIT) (Print PDF)

Heparin is used extensively in dialysis, most commonly for:


HIT occurs in 3% of patients who receive intravenous unfractionated heparin for treatment of deep vein thrombosis or pulmonary embolism.1 Lesser heparin exposures, such as prophylactic subcutaneous doses, flushes to maintain arterial catheter patency and even the tiny amounts of heparin that leach from coated vascular catheters, produce HIT in 0.5% of patients.

In HIT, platelet counts fall by more than 30% within 5 to 12 days after initial exposure to heparin. The degree of thrombocytopenia is highly variable. Thrombocytopenia often is moderate (80 to100 X 103/μL) and thus easily overlooked in an ICU or postoperative patient. However, modest thrombocytopenia may be the first clue to an impending HIT-related catastrophe. In one study 2, many of the patients with HIT had platelet counts at or below 20 X 103/μL, but bleeding was rare. Thirty percent to 75% of patients with HIT experience venous or arterial thromboemboli at the same time as or following the reduction in platelet count.(3 , 4)

Warkentin suggests that up to 25% of patients with heparin-induced thrombocytopenia may suffer some acute systemic reaction to heparin, such as chills, rigors, fever, hypertension, tachycardia, flushing, diaphoresis, nausea, myalgias, even transient global amnesia; these reactions are sometimes preceded by inflamed lesions at subcutaneous injection sites. (5, 6, 7) There have been reports of acute cardio-respiratory collapse from heparin since its introduction into clinical practice. (8, 9, 10 11)

Currently, dialysis treatments use saline flushes (generally ineffective) or regional citrate anticoagulation (dangerous expensive and labor intensive) to avoid using heparin.
Citrasate, a new acid concentrate for bicarbonate dialysis, is unique because it uses citrate in the dialysate. Citrate is a well-known anticoagulant that functions by binding calcium, thereby reducing the calcium available to participate in the blood clotting mechanism. Citrasate contains 2.4 mEq/L citric acid; well below the levels employed in regional citrate anticoagulation. In this concentration citrate dialysate has been successfully used for heparin-free dialysis of patients with antibodies to heparin (12).
Citrasate is a cost-effective alternative for high risk patients who tend to be more costly to treat. These patients can be impacted by blood loss plus treatment may require additional bloodlines, dialyzers and time. Citrasate is also ideal with patients who have bleeding risk factors, i.e. trauma, post-surgery, impending surgery/procedure.

References:
1. WARKENTIN TE, LEVINE MN, HIRSH JM, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight
heparin or unfractionated heparin. N Engl J Med 1995;332 (20):1330-5.
2. RICE L, HUFFMAN DM, LEVINE ML, et al. Heparin-induced thrombocytopenia/thrombosis syndrome: clinical manifestation and
insights. (Abstr) Blood 1986;68(5 Suppl 1):339
3. WARKENTIN TE, KELTON JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med 1996;101(5):502-7
4. RICE L, NGUYEN PH, VANN AR. Preventing complications in heparin-induced thrombocytopenia. Postgrad Med 2002;112(3)
5. WARKENTIN TE. Heparin-induced thrombocytopenia: A ten-year retrospective. Annu Rev Med 1999;50:129-147
6. WARKENTIN TE, SOUTAR RL, PANJU A, GINSBERG JS. Acute systemic reactions to IV bolus heparin therapy: characterization
and relationship to heparin-induced thrombocytopenia (Abstract). Blood 1992;80 (Suppl. 1):160a
7. LING E, WARKENTIN TE: Intraoperative heparin flushes and subsequent acute heparin-induced thrombocytopenia. Anesthesiol
1998;89:1567-1569.
8. CHERNOFF AI. Anaphylactic reaction following injection of heparin. N Engl J Med 1950;242:315-319
9. BERNSTEIN I. Anaphylaxis to heparin sodium. JAMA 1956;161:1379-1381
10. CURRY N, BARDANA EJ, PIROFSKY B. Heparin sensitivity: report of a case. Arch Intern Med 1973;132:744-745.
11. MIM MP, MANIAN P, RICE L. Acute cardio-respiratory collapse from heparin: a consequence of heparin-induced thrombocytopenia.
Eur J Haematol 2004;72: 366-369
12. TU A, AHMAD S, Heparin-free Hemodialysis with Citrate-Containing Dialysate in Intensive Care Patients. Dial & Trans 2000; 29:#10