Heparin

Brand Names: Heparin Flush; Heparin Lok-Pak; Heparin Novo; Heparin Porcine; Hepflush; Liquaemin Sodium; Sodium Heparin

Clinical Names: Heparin

Summary

generic name: Heparin

trade names: Heparin Flush®; Heparin Lok-Pak®; Heparin Novo®; Heparin Porcine; Hepflush®; Liquaemin Sodium; Sodium Heparin.

type of drug: Blood thinner, specifically a subcutaneous or intravenous anticoagulant, which prevents the formation of thrombin by accelerating the neutralization of activated coagulation factors by naturally occurring inhibitors.

used to treat: Prevention and management of intravascular clotting and embolism in patients susceptible to excessive clotting, especially following coronary occlusion or during surgery; heparin is also used in extra-corporeal circulation, i.e. heart-lung and renal dialysis machines and blood transfusions.

overview of interactions:
• nutrients affected by drug: 1,25-dihydroxyvitamin D (Vitamin D) and Calcium

• nutrient affected by drug: Potassium

• herbal constituent theoretically affecting drug performance and toxicity: Coumarin-containing Plants

Common herbs containing significant coumarin constituents:
Aesculus hippocastanum (Horse Chestnut seed)
Ammi visnaga (Visnaga)
Asperula odorata (Sweet Woodruff)
Galium odoratum (Bedstraw)
Melilotus spp. (Sweet Clover)
Trifolium pratense (Red Clover)

Note: See also Chinese Herbs topic: Blood-moving Herbs and Dan Shen

• herb affecting drug performance: Digitalis purpurea (Digitalis, Foxglove)

• herb affecting drug performance and toxicity: Ginkgo biloba (Ginkgo)

• herb group affecting drug performance and toxicity: Platelet Interactors

• nutrient affecting drug performance: Lentinas edodes (Shiitake)

• substance affecting drug performance: Alcohol



Interactions

nutrients affected by drug: 1,25-dihydroxyvitamin D (Vitamin D) and Calcium

• mechanism: Heparin interferes with the ability of the kidneys to activate vitamin D. Over time heparin causes bone loss, especially in the spine, hips, pelvis and legs.

• research: Majerus et al reported that use of heparin, at high doses, for a period of several months has been found to cause osteoporosis. Likewise both Wise and Hall, and later Haram et al, found that women who received heparin therapy during pregnancy experienced decreased bone density (Osteopenia). On the other hand, in one study nine women on heparin treatment received 6.46 g daily of a special calcium preparation OHC (ossein-hydroxyapatite-compound) over a period of six months and were compared to eleven women not receiving the bone protective treatment. In the OHC-group, good compliance was observed with no side effects and reduced back pain. Those taking the calcium preparation did not demonstrate the expected decreases in bone mass, while bone mass dropped significantly in the controls.
(Dahlman T, et al. Br J Obstet Gynaecol. 1990 Mar;97(3):221-228; Majerus PW, et al. 1996, 1346; Ringe JD, et al. Geburtshilfe Frauenheilkd 1992 Jul;52(7):426-429: Wise PH, Hall AS. BMJ 1980;281:110-111; Haram K, et al. Acta Obstet Gynecol Scand 1993;72:674-675.)

• nutritional support: There is no definitive pattern in the research confirming the benefits of supplementing vitamin D and calcium in individuals on heparin for any extended period. However, in the meantime, such supplementation could be beneficial and is not contraindicated. Individuals taking heparin should consult their physician and/or a healthcare provider trained in nutrition before they institute a program supplementation with vitamin D or calcium. With chronic use, tests can be done to measure l,25(OH)2 cholecalciferol levels. If low, calcitriol should be supplemented.

nutrient affected by drug: Potassium

• mechanism: Heparin therapy has been associated with hyperkalemia, i.e., abnormally high potassium levels.

• nutritional concerns: The clinical significance of changes in potassium levels due to heparin remains unclear. Individuals concerned about this side effect of heparin should consult their prescribing physician and/or pharmacist. Serum potassium levels are commonly measured as part of standard lab tests.

herbal constituent theoretically affecting drug performance and toxicity: Coumarin-containing Plants

• Common herbs containing significant coumarin constituents:
Aesculus hippocastanum (Horse Chestnut seed)
Ammi visnaga (Visnaga)
Asperula odorata (Sweet Woodruff)
Galium odoratum (Bedstraw)
Melilotus spp. (Sweet Clover)
Trifolium pratense (Red Clover)

• mechanism: Some authorities have suggested that coumarin-containing plants can theoretically exert an additive effect with pharmaceutical anticoagulants such as heparin. However, coumarins in plants have not been shown to be blood thinning and there is no evidence they are fermented into bioactive dicoumarol.

• herbal concern: Excessive bleeding would not be likely to appear unless relatively large doses of these herbs or their combinations were consumed for an extended period of time. The combination of these plants with anticoagulant drugs such as heparin theoretically increases the risk of excessive bleeding or other adverse side effects. In contrast, the effect of PAF interactor herbs on coagulation is much more probable and problematic.

• herbal concerns: Individuals taking heparin should avoid using herbs with anticoagulant action unless they have consulted with and are being monitored by their prescribing physician, preferably in concert with a healthcare professional trained in herbal medicine.

Note: See also Chinese Herbs topic: Blood-moving Herbs and Dan Shen

herb affecting drug performance: Digitalis purpurea (Digitalis, Foxglove)

• mechanism: Digoxin has been reported to interfere with the anticoagulant activity of heparin. The herb Digitalis also contains cardiac glycosides which may reduce the therapeutic activity of heparin by interfering with the drug's anticoagulant action. The serum protein binding of digitoxin and digoxin is particularly a concern in uremic patients under treatment with hemodialysis.
(Hooymans PM, Merkus FW. Clin Pharm. 1985 Jul-Aug;4(4):404-413; Storstein L, Janssen H. Clin Pharmacol Ther. 1976 Jul;20(1):15-23.)

• herbal concern: Individuals undergoing heparin therapy should avoid consumption of Digitalis and products containing digoxin or digitoxin. Medical herbalists rarely prescribe Digitalis and its usage is restricted by law in many places. Whether or not taking heparin, individuals are warned against taking Digitalis in any form unless they are under the direct supervision of a physician.

herb affecting drug performance and toxicity: Ginkgo biloba (Ginkgo)

• mechanism: Gingko may reduce the tendency for platelet aggregation, i.e., the ability for platelets to stick together. Consequently individuals taking Gingko may have an increased incidence of bleeding and may find that they bruise more easily or even spontaneously. In some respects these are side effects of the desired action of increasing peripheral circulation and decreasing clotting.
(Kleijnen J, Knipschild P. Lancet 1992;340:1136-1139.)

• reports: Rowin and Rosenblatt and their associates have reported cases of spontaneous bleeding that occurred at the same time the patients were taking Gingko extracts. However, while these associations were observed no causal relationship was confirmed. Matthews reported the case of one individual who experienced increased bleeding, specifically intracerebral hemorrhage, after they began taking Gingko while also using warfarin, another anticoagulant medication.
(Rowin J, Lewis SL. Neurology 1996 Jun;46(6):1775-1776; Rosenblatt M, Mindel J. New Engl J Med 1997 Apr 10;336(15):1108; Matthews MK. Neurology 1998 Jun;50(6):1933-1934.)

• herbal concerns: Individuals taking heparin should avoid taking Gingko unless they have consulted with and are being monitored by their prescribing physician, preferably in concert with a healthcare profressional trained in herbal medicine.

herb group affecting drug performance and toxicity: Platelet Interactors

nutrient affecting drug performance: Lentinas edodes (Shiitake)

• reports and research: According to Hobbs a watery extract of the whole shiitake has been reported to hinder blood coagulation. However, Otsuka et al found that a mixture consisting of dried Shiitake mushrooms treated with wet-heating and fructo-oligosaccharides produced an anti-thrombotic action in rats were evaluated.
(Hobbs C. 1995, 125-128; Otsuka M, et al. Yakugaku Zasshi. 1996 Feb;116(2):169-173.)

• nutritional/herbal concern: Individuals taking heparin, warfarin or other anticoagulant medicines should refrain from consuming Shiitake beyond occasional use in foods until they have consulted with their prescribing physician and/or a healthcare professional trained in herbal prescribing.

substance affecting drug performance: Alcohol

• research: The consumption of alcohol by individuals undergoing heparin therapy has been associated with increased risk of excessive bleeding.
(Holt GA. 1998, 127.)

• dietary concerns: Individuals taking heparin should avoid the consumption of alcohol, or alcohol-containing substances.


Please read the disclaimer concerning the intent and limitations of the information provided here.
Do not rely solely on the information in this article.

The information presented in Interactions is for informational and educational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, case reports, and/or traditional usage with sources as cited in each topic. The results reported may not necessarily occur in all individuals and different individuals with the same medical conditions with the same symptoms will often require differing treatments. For many of the conditions discussed, treatment with conventional medical therapies, including prescription drugs or over-the-counter medications, is also available. Consult your physician, an appropriately trained healthcare practitioner, and/or pharmacist for any health concern or medical problem before using any herbal products or nutritional supplements or before making any changes in prescribed medications and/or before attempting to independently treat a medical condition using supplements, herbs, remedies, or other forms of self-care.



References

Aarskog D, Aksnes L, Lehmann V. Low 1,25-dihydroxyvitamin D in heparin-induced osteopenia. Lancet 1980 Sep 20;2(8195 Pt 1):650-651. (Letter)

Aarskog D, Aksnes L, Markestad T, Ulstein M, Sagen N. Heparin-induced inhibition of 1,25-dihydroxyvitamin D formation. Am J Obstet Gynecol 1984 Apr 15;148(8):1141-1142.

Camici M. Dialysis-associated bone disease. JAMA 1986 Sep 19;256(11):1447. (Letter)

Dahlman T, Lindvall N, Hellgren M. Osteopenia in pregnancy during long-term heparin treatment: a radiological study post partum. Br J Obstet Gynaecol. 1990 Mar;97(3):221-228.
Abstract: Osteopenia, sometimes with compression fractures of the spine, is a side-effect of long-term heparin treatment. The frequency is unknown. In this study, 70 women were given subcutaneous heparin as therapy for, or prophylaxis against, thromboembolism during pregnancy. All, except two, were examined by X-ray of the spine and hip first week post partum. The duration of treatment and the dosage of heparin varied. There were 12 (17%) with obvious osteopenia, including two women with multiple fractures of the spine (3%). Re-examination 6-12 months post partum showed that the changes were reversible in most cases. Another 18 women were examined about three years after heparin treatment during pregnancy. No obvious osteopenia was found among them or in a control group of 30 women examined in the first week post partum. The degree of osteopenia was not correlated with either the heparin dose or the duration of treatment. Women treated with heparin in consecutive pregnancies do not seem to have an increased risk of osteopenia.

Haram K, Hervig T, Thordarson H, Aksnes L. Osteopenia caused by heparin treatment in pregnancy. Acta Obstet Gynecol Scand 1993 Nov;72(8):674-675.
Abstract: A case is reported of severe osteopenia caused by heparin treatment of thrombosis in the eleventh week of pregnancy followed by heparin prophylaxis (5000 IU three times daily) during pregnancy and lactation. The mother complained of back pain during the last two weeks of pregnancy. Six weeks post partum, generalized osteopenia in the skeleton was diagnosed and a compression fracture of the body of the sixth thoracic vertebra. During pregnancy the mother had relatively low serum concentrations of 1,25(OH)2D, the active metabolite of vitamin D, and six weeks after delivery the serum concentration had fallen to about 50% of the lowest reference level. Eight and fourteen weeks after delivery, when heparin treatment had been discontinued, the serum concentrations of 1,25(OH)2D were within the reference range for non-pregnant adults.

Hobbs C. Medicinal Mushrooms. Santa Cruz, CA: Botanica Press, 1995, 125-128.

Holt GA. Food and Drug Interactions. Chicago: Precept Press, 1998, 127.

Hooymans PM, Merkus FW. Current status of cardiac glycoside drug interactions. Clin Pharm. 1985 Jul-Aug;4(4):404-413. (Review)

Kleijnen J, Knipschild P. Ginkgo biloba. Lancet 1992;340:1136-1139.

Majerus PW, Broze GJ Jr, Miletich JP, Tollefsen DM. Anticoagulant, thrombolytic, and antiplatelet drugs. In: Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 9th ed. New York: McGraw-Hill 1996, 1346.

Matthews MK Jr. Association of Ginkgo biloba with intracerebral hemorrhage. Neurology 1998 Jun;50(6):1933-1934.

Miller LG, Murray WJ, eds. Herbal Medicinals: A Clinician’s Guide. New York: Pharmaceutical Products Press, 1999, 313-315.

Nelson-Piercy C. Heparin-induced osteoporosis in pregnancy. Lupus 1997;6(6):500-504. (Review)

Newall CA, Anderson LA, Phillipson JD. Herbal Medicines: A Guide for Health-Care Professionals. London: The Pharmaceutical Press, 1996, 135-37.

Otsuka M, Shinozuka K, Hirata G, Kunitomo M. [Influences of a shiitake (Lentinus edodes)-fructo-oligosaccharide mixture (SK-204) on experimental pulmonary thrombosis in rats]. Yakugaku Zasshi. 1996 Feb;116(2):169-173. [Article in Japanese]
Abstract: Effects of the mixture (SK-204) consisting of dried shiitake mushroom (Lentinus edodes) treated with wet-heating and fructo-oligosaccharides (7:3) on the experimental models of pulmonary thrombosis induced by lactic acidosis in rats were evaluated. Chronic oral administration (10 weeks) of SK-204 significantly prevented the thrombus formation on this thrombosis model. However, decreases in the numbers of platelet and fibrinogen level by lactate were not changed by SK-204. These results suggest that SK-204 have an anti-thrombotic action, which is due to neither the inhibition of platelet aggregation nor coagulation, but probably due to the promotion of fibrinolysis and thrombolysis.

Ringe JD, Becker K. [Osteoporosis caused by long term heparin therapy]. Med Monatsschr Pharm 1985 Mar;8(3):80-83. [Article in German]

Ringe JD, Keller A. [Risk of osteoporosis in long-term heparin therapy of thromboembolic diseases in pregnancy: attempted prevention with ossein-hydroxyapatite]. Geburtshilfe Frauenheilkd 1992 Jul;52(7):426-429. [Article in German] Abstract: Generalized idiopathic osteoporosis and transient osteoporosis of the hip are both rare complications of pregnancy. More frequently, long-term heparin administration to treat deep thrombosis in the legs or pelvis may lead to substantial decreases in bone mass and consequently increased risk of osteoporosis. Therapeutic studies with the aim to counteract the osteoporosis inducing effect of heparins, have not been published to date. In the special situation of pregnancy, most medications used for osteoporosis are contraindicated. In our open randomised study, 9 women on heparin-treatment received daily 6.46 g of the bone preparation OHC (ossein-hydroxyapatite-compound) over a period of 6 months and were compared to 11 women without bone protective treatment. In the OHC-group, good compliance was observed with no side effects and reduced back pain. Bone mass did not change significantly, whilst it dropped significantly statistically in the controls.

Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of Ginkgo biloba extract. New Engl J Med 1997 Apr 10;336(15):1108.

Rowin J, Lewis SL. Spontaneous bilateral subdural hematoma with chronic Gingko biloba ingestion. Neurology 1996 Jun;46(6):1775-1776.

Rupp WM, McCarthy HB, Rohde TD, Blackshear PJ, Goldenberg FJ, Buchwald H. Risk of osteoporosis in patients treated with long-term intravenous heparin therapy. Curr Surg 1982 Nov;39(6):419-422.

Storstein L, Janssen H. Studies on digitalis. VI. The effect of heparin on serum protein binding of digitoxin and digoxin. Clin Pharmacol Ther. 1976 Jul;20(1):15-23.
Abstract: The aim of the present study was to investigate the nature of the previously reported changes in the serum protein binding of digitoxin and digoxin in uremic patients under treatment with hemodialysis. Kinetic studies on protein binding during hemodialysis showed that the free fraction of digitoxin rose from 2.6% to 6.9% after 5 min of hemodialysis and remained elevated during the dialyzing period. Free digoxin rose from hemodialysis and remained elevated during the dialyzing period. Free digoxin rose from 78.3% to 87.1% during the same period. In vitro hemodialysis experiments showed that such changes occurred only in vivo. Injection of heparin (5,000 IU) to control subjects produced similar kinetic changes in the protein binding of digitoxin and digoxin. Free fatty acids changed in the same way. These results indicate that the heparin-induced release of free fatty acids causes displacement of digitoxin and digoxin from their albumin-binding sites. Patients on hemodialysis have lower serum levels of digitoxin and cardioactive metabolites (mean, 8.9 ng/ml) than control patients (mean, 16.7 ng/ml) (p less than 0.005) on similar doses (mean, 0.085 mg/day). They should be maintained on the same digotoxin doses as uremic and control patients, but serum digitoxin levels should be adjusted to 10 to 15 ng/ml in hemodialysis patients compared to 15 to 25 ng/ml in uremic patients and in patients with normal renal function.

Threlkeld DS, ed. Blood Modifiers, Anticoagulants, Heparin. In: Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Jun 1997.

Wise PH, Hall AJ. Heparin-induced osteopenia in pregnancy. Br Med J 1980 Jul 12;281(6233):110-111.
Abstract: Multiple vertebral compression fractures occurred in a pregnant woman receiving heparin over nine months. This phenomenon may be more common than is clinically recognised and warrants careful re-examination of the indications and method of administration of anti-coagulants during pregnancy.