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Heparin Disease Interactions

There are 7 disease interactions with heparin:

Major

Anticoagulants (applies to heparin) peptic ulcer disease

Major Potential Hazard, Moderate plausibility. Applicable conditions: Bleeding

Anticoagulants are contraindicated in patients with active major bleeding or those patients at risk for hemorrhage. Hemorrhage due to heparin derivatives may be treated with protamine sulfate 1%. However, protamine sulfate may not completely neutralize the anti- Factor Xa activity.

References

  1. "Product Information. Heparin Sodium (heparin)." Lilly, Eli and Company, Indianapolis, IN.
  2. "Product Information. Fragmin (dalteparin)." Pharmacia and Upjohn, Kalamazoo, MI.
  3. "Product Information. Lovenox (enoxaparin)." Rhone-Poulenc Rorer, Collegeville, PA.
  4. Hirsh J, Fuster V "Guide to anticoagulant therapy. 1. Heparin." Circulation 89 (1994): 1449-68
  5. "Product Information. Orgaran (danaparoid)." Organon, West Orange, NJ.
  6. Walker AM, Jick H "Predictors of bleeding during heparin therapy." JAMA 244 (1980): 1209-12
  7. Oates JA, Wood AJJ "Heparin." N Engl J Med 324 (1991): 1565-74
  8. Nieuwenhuis HK, Albada J, Banga JD, Sixma JJ "Identification of risk factors for bleeding during treatment of acute venous thromboembolism with heparin or low molecular weight heparin." Blood 78 (1991): 2337-43
  9. Nieuwenhuis HK, Albada J, Banga JD, Sixma JJ "Identification of risk factors for bleeding during treatment of acute venous thromboembolism with heparin or low molecular weight heparin." Blood 78 (1991): 2337-43
  10. Breddin HK "Low molecular weight heparins and bleeding." Semin Thromb Hemost 15 (1989): 401-4
  11. Sugiyama T, Itoh M, Ohtawa M, Natsuga T "Study on neutralization of low molecular weight heparin (LHG) by protamine sulfate and its neutralization characteristics." Thromb Res 68 (1992): 119-29
View all 11 references
Major

Heparin (applies to heparin) active bleeding

Major Potential Hazard, High plausibility. Applicable conditions: Peptic Ulcer, Coagulation Defect, Infectious Endocarditis, Abnormal Uterine Bleeding, Colonic Ulceration, Liver Disease, Ulcerative Colitis, Diverticulitis, Myeloproliferative Disorder

The use of heparin is contraindicated in patients with uncontrollable active bleeding, except when the bleeding is due to disseminated intravascular coagulation. Hemorrhage can occur at virtually any site in patients receiving heparin. An unexplained drop in hematocrit or blood pressure, or any other unexplained symptom, should lead to serious consideration of a hemorrhagic event. Therapy with heparin should be used with extreme caution in patients with known bleeding disorders or disease states that may predispose to hemorrhage during heparin administration, including hemophilia, thrombocytopenia, certain vascular purpuras, ulcerative gastrointestinal lesions, diverticulitis, ulcerative colitis, severe liver disease, subacute bacterial endocarditis, severe hypertension, myeloproliferative disorders, and threatened abortion. Blood coagulation tests (e.g., whole blood clotting time, activated partial thromboplastin time) should be performed at appropriate intervals during full-dose heparin administration. In addition, periodic platelet counts, hematocrits, and tests for occult blood in stool are recommended during the entire course of heparin therapy. There is usually no need to monitor coagulation parameters in patients receiving low-dose heparin, except in patients undergoing major surgery. For low molecular weight heparin (LMWH), coagulation tests such as prothrombin time (PT) and aPTT are relatively insensitive measures of LMWH activity and not suitable for routine monitoring. Anti-Factor Xa may be used to monitor the anticoagulant effect of LMWH in patients with significant renal impairment, abnormal coagulation parameters, or bleeding during therapy.

References

  1. Sugiyama T, Itoh M, Ohtawa M, Natsuga T "Study on neutralization of low molecular weight heparin (LHG) by protamine sulfate and its neutralization characteristics." Thromb Res 68 (1992): 119-29
  2. Breddin HK "Low molecular weight heparins and bleeding." Semin Thromb Hemost 15 (1989): 401-4
  3. Nieuwenhuis HK, Albada J, Banga JD, Sixma JJ "Identification of risk factors for bleeding during treatment of acute venous thromboembolism with heparin or low molecular weight heparin." Blood 78 (1991): 2337-43
  4. Chong BH, Magnani HN "Orgaran in heparin-induced thrombocytopenia." Haemostasis 22 (1992): 85-91
  5. Nicholson CD, Meuleman DG, Magnani HN, Egberts JF, Leibowitz DA, Spinler SA, Cziraky MJ "Danaparoid is not a low-molecular-weight heparin." Am J Hosp Pharm 51 (1994): 2049-50
  6. Bergqvist D, Burmark US, Frisell J, Hallbook T, Lindblad B, Risberg B, Torngren S, Wallin G "Prospective double-blind comparison between Fragmin and conventional low-dose heparin: thromboprophylactic effect and bleeding complications." Haemostasis 16 Suppl 2 (1986): 11-8
  7. Magnani HN "Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with orgaran (Org 10172) [published erratum appears in Thromb Haemost 1993 Dec 20;70(6):1072]." Thromb Haemost 70 (1993): 554-61
  8. "Product Information. Heparin Sodium (heparin)." Lilly, Eli and Company, Indianapolis, IN.
  9. "Product Information. Lovenox (enoxaparin)." Rhone-Poulenc Rorer, Collegeville, PA.
  10. "Product Information. Orgaran (danaparoid)." Organon, West Orange, NJ.
  11. "Product Information. Fragmin (dalteparin)." Pharmacia and Upjohn, Kalamazoo, MI.
  12. de Valk HW, Banga JD, Wester JW, Brouwer CB, van Hessen MW, Meuwissen OJ, Hart HC, Sixma JJ, Nieuwenhuis HK "Comparing subcutaneous danaparoid with intravenous unfractionated heparin for the treatment of venous thromboembolism. A randomized controlled trial." Ann Intern Med 123 (1995): 1-9
View all 12 references
Major

Heparin (applies to heparin) hypertension

Major Potential Hazard, Moderate plausibility.

Heparin should be used with extreme caution in patients with uncontrolled or severe hypertension as these conditions may predispose the patient to hemorrhage during heparin administration. Blood coagulation tests (e.g., whole blood clotting time, activated partial thromboplastin time) should be performed at appropriate intervals during full-dose heparin administration. In addition, periodic platelet counts, hematocrits, and tests for occult blood in stool are recommended during the entire course of heparin therapy. Clinical monitoring of blood pressure is recommended.

Major

Heparin (applies to heparin) prematurity

Major Potential Hazard, Moderate plausibility. Applicable conditions: Prematurity/Underweight in Infancy

The use of certain heparin sodium injections and heparin lock flush solutions is considered by the manufacturers to be contraindicated in premature infants and infants of low birth weight. Some formulations of these drugs contain benzyl alcohol which, in bacteriostatic saline intravascular flush and endotracheal tube lavage solutions, has been associated with fatalities and severe respiratory and metabolic complications in low-birthweight premature infants. Symptoms include a striking onset of gasping respiration, hypotension, bradycardia, and cardiovascular collapse. The manufacturers further recommend that use of these products be avoided in all neonates whenever possible. Neonates requiring heparin lock flush solution should be given a preservative-free formulation. Nevertheless, many experts feel that, in the absence of benzyl alcohol-free equivalents, the amount of the preservative present in these formulations should not necessarily preclude their use if they are clearly indicated. The American Academy of Pediatrics considers benzyl alcohol in low doses (such as when used as a preservative in some medications) to be safe for newborns.

The use of heparin for maintaining patency of umbilical artery catheters may be associated with an increased risk of germinal matrix intraventricular hemorrhage in low-birthweight neonates. Although a definitive causal relationship has not been established, caution may be appropriate when heparin lock flush solutions are used.

Due to the risk of overdose, heparin lock flush solutions containing 100 units/mL should not be used in neonates, particularly those who are premature or have low birthweight.

Major

Heparin (applies to heparin) renal dysfunction

Major Potential Hazard, High plausibility.

Systemic exposure and the risk of bleeding may be increased when heparin is used in the presence of severe renal impairment. Therapy with heparin should be administered cautiously in patients with significantly impaired renal function. A reduction in dosage may be necessary.

Major

Heparin (applies to heparin) thrombocytopenia

Major Potential Hazard, High plausibility. Applicable conditions: Heparin-Induced Thrombocytopenia

The use of heparin is contraindicated in patients with severe thrombocytopenia. Acute thrombocytopenia can occur in patients receiving heparin, with a reported incidence of up to 30%. Platelet counts should be obtained before and periodically during heparin administration, including regular and repeated use of heparin flush solutions if given for longer than 5 days. Mild thrombocytopenia with counts above 100,000/mm3 may remain stable or reverse despite continued heparin administration. However, thrombocytopenia of any degree should be closely monitored. Therapy should be discontinued if the count falls below 100,000/mm3 or if recurrent thrombosis develops, and an alternative, nonheparin anticoagulant (e.g., argatroban, bivalirudin, lepirudin) administered if necessary. Heparin-induced thrombocytopenia (HIT) is a serious antibody-mediated reaction resulting from irreversible aggregation of platelets. HIT may progress to the development of venous and arterial thromboses, a condition referred to as heparin-induced thrombocytopenia and thrombosis (HITT). Thrombotic events may also be the initial presentation for HITT, and may include deep vein thrombosis, pulmonary embolism, cerebral vein thrombosis, limb ischemia, stroke, myocardial infarction, mesenteric thrombosis, renal artery thrombosis, skin necrosis, gangrene of the extremities that may lead to amputation, and possibly death. Both HIT and HITT can occur up to several weeks after the discontinuation of heparin therapy. Patients presenting with thrombocytopenia or thrombosis after discontinuation of heparin should be evaluated for HIT and HITT. Following an episode, any future use of heparin should be avoided, and use of low-molecular weight heparin should consider the potential for cross-reactivity with the HIT antibody and approached with extreme caution, if not otherwise contraindicated.

References

  1. Kelton JG, Sheridan D, Santos A, et al "Heparin-induced thrombocytopenia: laboratory studies." Blood 72 (1988): 925-30
  2. Magnani HN "Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with orgaran (Org 10172) [published erratum appears in Thromb Haemost 1993 Dec 20;70(6):1072]." Thromb Haemost 70 (1993): 554-61
  3. Berkowitz N, Beckman J "Heparin-induced thrombocytopenia." N Engl J Med 333 (1995): 1006
  4. Cines DB, Kaywin P, Bina M, et al "Heparin-associated thrombocytopenia." N Engl J Med 303 (1980): 788-95
  5. Eichinger S, Kyrle PA, Brenner B, Wagner B, Kapiotis S, Lechner K, Korninger HC "Thrombocytopenia associated with low-molecular-weight heparin" Lancet 337 (1991): 1425-6
  6. Kleinschmidt S, Seyfert UT "Heparin-associated thrombocytopenia (HAT) - still a diagnostic and therapeutical problem in clinical practice." Angiology 46 (1995): 37-44
  7. Rissieri DA, Wong WM, Gockerman JP "Thrombocytosis associated with low-molecular-weight heparin." Ann Intern Med 125 (1996): 157
  8. Ramakrishna R, Manoharan A, Kwan YL, Kyle PW "Heparin-induced thrombocytopenia: cross-reactivity between standard heparin, low molecular weight heparin, dalteparin (fragmin) and heparinoid, danaparoid (orgaran)." Br J Haematol 91 (1995): 736-8
  9. Yamamoto S, Koide M, Matsuo M, Suzuki S, Ohtaka M, Saika S, Matsuo T "Heparin-induced thrombocytopenia in hemodialysis patients." Am J Kidney Dis 28 (1996): 82-5
  10. "Product Information. Orgaran (danaparoid)." Organon, West Orange, NJ.
  11. Bell WR, Royall RM "Heparin-associated thrombocytopenia: a comparison of three heparin preparations." N Engl J Med 303 (1980): 902-7
  12. Platell CF, Tan EG "Hypersensitivity reactions to heparin: delayed onset thrombocytopenia and necrotizing skin lesions." Aust N Z J Surg 56 (1986): 621-3
  13. Hougardy N, Machiels JP, Ravoet C "Heparin-induced thrombocytopenia." N Engl J Med 333 (1995): 1007
  14. Chong BH, Magnani HN "Orgaran in heparin-induced thrombocytopenia." Haemostasis 22 (1992): 85-91
  15. Tezcan AZ, Tezcan H, Gastineau DA, Armitage JO, Haire WD "Heparin-induced thrombocytopenia after bone marrow transplantation: report of two cases." Bone Marrow Transplant 14 (1994): 487-90
  16. Lecompte T, Luo SK, Stieltjes N, Lecrubier C, et al "Thrombocytopenia associated with low-molecular-weight heparin." Lancet 338 (1991): 1217
  17. Schiele F, Vuillemenot A, Kramarz P, Kieffer Y, Anguenot T, Bernard Y, Bassand JP "Use of recombinant hirudin as antithrombotic treatment in patients with heparin-induced thrombocytopenia." Am J Hematol 50 (1995): 20-5
  18. Warkentin TE, Hirsh J, Kelton JG "Heparin-induced thrombocytopenia." N Engl J Med 333 (1995): 1007
  19. Bergqvist D, Burmark US, Frisell J, Hallbook T, Lindblad B, Risberg B, Torngren S, Wallin G "Prospective double-blind comparison between Fragmin and conventional low-dose heparin: thromboprophylactic effect and bleeding complications." Haemostasis 16 Suppl 2 (1986): 11-8
  20. Bleasel JF, Rasko JE, Rickard KA, Richards G "Acute adrenal insufficiency secondary to heparin-induced thrombocytopenia-thrombosis syndrome." Med J Aust 157 (1992): 192-3
  21. Peters FPJ, Doevendans PAFM, Erdkamp FLG, Vanderent FWC, Deheer F "Low molecular weight heparin-induced thrombocytopenia and thrombosis." Eur J Haematol 56 (1996): 329-30
  22. Monreal M, Lafoz E, Salvador R, Roncales J, Navarro A "Adverse effects of three different forms of heparin therapy: thrombocytopenia, increased transaminases, and hyperkalaemia." Eur J Clin Pharmacol 37 (1989): 415-8
  23. Rice P, Dace S, Mcmullin MF, Clements WDB "Heparin induced thrombocytopenia causing life-threatening postoperative haemorrhage." Br J Clin Pract 50 (1996): 404-5
  24. Slocum MM, Adams JG, Teel R, Spadone DP, Silver D "Use of enoxaparin in patients with heparin-induced thrombocytopenia syndrome." J Vasc Surg 23 (1996): 839-43
  25. Gruel Y, Lang M, Darnige L, Pacouret G, Dreyfus X, Leroy J, Charbonnier B "Fatal effect of re-exposure to heparin after previous heparin- associated thrombocytopenia and thrombosis ." Lancet 336 (1990): 1077-8
  26. Shumate MJ "Heparin-induced thrombocytopenia." N Engl J Med 333 (1995): 1006-7
  27. Monreal M, Lafoz E, Salvador R, Roncales J, Navarro A "Adverse effects of three different forms of heparin therapy: thrombocytopenia, increased transaminases, and hyperkalaemia." Eur J Clin Pharmacol 37 (1989): 415-8
  28. "Product Information. Lovenox (enoxaparin)." Rhone-Poulenc Rorer, Collegeville, PA.
  29. Warkentin TE, Hayward CP, Smith CA, et al "Determinants of donor platelet variability when testing for heparin-induced thrombocytopenia." J Lab Clin Med 120 (1992): 371-9
  30. Force RW "Heparin-induced thrombocytopenia." Am J Health Syst Pharm 52 (1995): 2528
  31. Sandler RM, Seifer DB, Morgan K, Pockros PJ, Wypych J, Weiss LM, Schiffman S "Heparin-induced thrombocytopenia and thrombosis: detection and specificity of a platelet-aggregating IgG." Am J Clin Pathol 83 (1985): 760-4
  32. Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, Kelton JG "Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin." N Engl J Med 332 (1995): 1330-5
  33. Luzzatto G, Cordiano I, Patrassi G, Fabris F "Heparin-induced thrombocytopenia: discrepancy between the presence of IgG cross-reacting in vitro with fraxiparine and its successful clinical use." Thromb Haemost 75 (1996): 211-2
  34. Rizzieri DA, Wong WM, Gockerman JP "Thrombocytosis associated with low-molecular-weight heparin." Ann Intern Med 125 (1996): 157
  35. Kikta MJ, Keller MP, Humphrey PW, Silver D, Towne JB, Tsapogas M "Can low molecular weight heparins and heparinoids be safely given to patients with heparin-induced thrombocytopenia syndrome?" Surgery 114 (1993): 705-10
  36. Balestra B, Quadri P, Biasiutti FD, Furlan M, Lammle B "Low molecular weight heparin-induced thrombocytopenia and skin necrosis distant from injection sites." Eur J Haematol 53 (1994): 61-3
  37. Chong BH "Heparin-induced thrombocytopenia." Aust N Z J Med 22 (1992): 145-52
  38. Munver R, Schulman IC, Wolf DJ, Rosengart TK "Heparin-induced thrombocytopenia and thrombosis: presentation after cardiopulmonary bypass." Ann Thorac Surg 58 (1994): 1764-6
  39. "Product Information. Heparin Sodium (heparin)." Lilly, Eli and Company, Indianapolis, IN.
View all 39 references
Moderate

Heparin (applies to heparin) hyperkalemia

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: Diabetes Mellitus, Renal Dysfunction, Acidosis

Heparin can suppress adrenal secretion of aldosterone and cause hyperkalemia, particularly in patients with diabetes mellitus, chronic renal failure, preexisting metabolic acidosis, or elevated serum potassium levels. The risk of hyperkalemia appears to increase with duration of therapy, but is usually reversible. Therapy with heparin should be administered cautiously in patients with preexisting hyperkalemia or risk factors for hyperkalemia. Serum potassium should be measured before initiating treatment and also during treatment, especially if heparin is given for longer than 7 days.

Heparin drug interactions

There are 215 drug interactions with heparin

Heparin alcohol/food interactions

There is 1 alcohol/food interaction with heparin

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.