Anticoagulation

Thrombophilias in pregnancy

The thrombophilias are a group of disorders that promote blood clotting. Most women with a thrombophilia have healthy pregnancies. However, pregnant women with a thrombophilia may be more likely than other pregnant women to develop a Venous thrombosis or certain pregnancy complications. Even pregnant women without a thrombophilia may be more likely than non-pregnant women to develop a VTE. This is due to normal pregnancy-related changes in blood clotting that limit blood loss during labor and delivery. However, studies suggest that up to 80 percent of pregnant women who develop a pulmonary embolus or other VTE have an underlying thrombophilia. Pulmonary embolus is the leading cause of maternal death in the United States.

The thrombophilias also may contribute to pregnancy complications including:Fetal loss. This may occur late in the first trimester (miscarriage) or in the second or third trimesters (stillbirth). and Placental abruption. In this condition, the placenta peels away from the uterine wall, partially or completely, before delivery. .Some pregnant women with a thrombophilia are treated with low moecular weight heparins, such as Lovenox. However, not all women with a thrombophilia need treatment during pregnancy. A woman and her health care provider should discuss her individual risks of blood clots and pregnancy complications and the severity of her thrombophilia before deciding whether or not she needs treatment.

In general, treatment is not recommended for most pregnant women with one of the less severe thrombophilias (such as factor V Leiden or prothrombin mutations) who have no personal or family history of blood clots or pregnancy complications. The risk of VTE is less than 0.5 percent (1 in 200) in pregnant women with factor V Leiden with no personal or strong family history of VTE.

While MTHFR heterozygosity itself does not increse risk of thrombosis or fetal compications, when combined with the prothrombin mutation, the risk incrases exponentially.

  1. Lockwood, C.J. and Bauer, K.A. Inherited Thrombophilias in Pregnancy. UpToDate, April, 13, 2006.
  2. Lockwood, C.J. Preventing VTE: Part 3—The Pregnant Patient. Contemporary Ob/Gyn, May 2005, pages 11-12.
  3. James, A.H., et al. Thrombosis During Pregnancy and the Postpartum Period. American Journal of Obstetrics and Gynecology, volume 193, number 1, July 2005, pages 216-219.
  4. American College of Obstetricians and Gynecologists (ACOG). Thromboembolism in Pregnancy. ACOG Practice Bulletin, number 19, August 2000.
  5. American College of Obstetricians and Gynecologists (ACOG). Antiphospholipid Syndrome. ACOG Practice Bulletin, number 68, November 2005.

Generic versus proprietary Warfarin

Whether generic and proprietary wrafarin is interchangeable has been investigated. Multiple n-of-1 randomized, double-blind, crossover trials switched outpatients (N = 7) between a generic warfarin formulation (Apo-warfarin) and Coumadin over 30 weeks. Study patients took each drug for five 3-week periods, with international normalized ratio (INR) measurements taken twice per period. Inter- and intrapatient differences between generic warfarin and Coumadin were compared, and overall study patient results were compared with those of a Coumadin control group.
There were no differences between warfarin products in terms of mean INR results or number of dosage adjustments required. There also was no difference in INR variation based on warfarin formulation (p > 0.69), nor was a patient and warfarin interaction found (p > 0.81). The INR results were not influenced by whether patients were maintained on Coumadin only (control group) or interchanged between Coumadin and generic warfarin (p = 0.98). Bongiorno RA, Nutescu EA. Generic warfarin: implications for clinical practice and perceptions of anticoagulation providers. Semin Thromb Hemost. 2004;30:619-626.

Halkin H, Shapiro J, Kurnik D, Loebstein R, Shalev V, Kokia E. Increased warfarin doses and decreased international normalized ratio response after nationwide generic switching. Clin Pharmacol Ther. 2003;74:215-221.

Witt DM, Tillman DJ, Evans CM. Evaluation of the clinical and economic impact of a brand name-to-generic warfarin sodium conversion program. Pharmacotherapy. 2003;23:360-368.

Jennifer A Pereira et al, Are Brand-Name and Generic Warfarin Interchangeable? Multiple N-of-1 Randomized, Crossover Trials The Annals of Pharmacotherapy: Vol. 39, No. 7, pp. 1188-1193.

Anticoagulation in cancer patients - guidelines

Pulmonary emboli is an indication for long term anticoagulation. Although generally oral warfarin is used, it is now recognized that it is not as effective in patients with thromboses secondary to cancer as are the low molecular weight heparins, such as Lovenox.

Low Molecular Weight Heparins are used for the prophylaxis or treatment of deep vein thrombosis. The decision to use LMWH instead of standard heparin or warfarin will depend upon the clinical scenario and individual patient factors such as risk of bleeding or availability of venous access.

Several studies have shown that patients with malignancy and thrombosis do not respond well to warfarin and many of them have recurrent DVT on warfarin. The National Comprehensive Cancer Network has issued its first guidelines for how to prevent deep vein thrombosis (DVT) in cancer patients and how to treat a DVT. The guidelines listed the following agents for anticoagulation:

Unfractionated heparin: 5,000 units subcutaneously three times a day.
Low molecular weight heparin, dosed according to standard operating procedures of individual institutions, with either dalteparin, enoxaparin or tinzaparin.
Pentasaccharide, fondaparinux, 2.5 mg subcutaneous daily.

The guidelines were revealed at the 11th annual conference of the NCCN -- a consortium of 19 of the leading cancer centers in the country. They included recommendations for prophylaxis of venous thromboembolism in cases of patients with cancer or who are suspected of cancer. If they do not have contraindication for anticoagulation, then therapy was suggested with or without sequential compression devices. If there is a contraindication for anticoagulant therapy then use of compression devices, including graduated compression stocking, were considered.

For initial treatment of DVT or PE, either UFH or LMWH should be administered. For postoperative patients, an agent such as UFH, which has a short half life and is readily reversible, may be preferable. For more stable patients who are not at high risk for bleeding, LMWH is probably the treatment of choice.

Chronic VTE therapy with anticoagulants in cancer patients is a challenge. Many anticancer medications interact with oral anticoagulants (eg, warfarin), he added, and make it difficult to control the level of anticoagulation, particularly in cancer patients with more extensive disease. In a study of patients with and without cancer receiving oral anticoagulants, the VTE recurrence rate and risk of bleeding were substantially higher in patients with advanced cancer, particularly in the first 2 months of therapy. Recent results from the CLOT trial showed that the incidence of VTE recurrence was significantly lower in patients with advanced cancer receiving dalteparin (Fragmin) versus those receiving oral anticoagulation therapy over a 6-month period. The bottom line is that LMWH should be strongly considered in patients who have advanced metastatic cancer (Lee AY et al. N Engl J Med 2003;349:146–153).New guideline recommendations have been released for the use of anticoagulation in the prevention and treatment of venous thromboembolism (VTE) in patients with cancer. The guidelines, which were prepared by an international panel of researchers and are published in the October 29 Early Release Articles issue and were published in the December 1, 2007 issue of the Journal of Clinical Oncology.
The ASCO panel was a mix of world-famous experts in thrombosis and methodology, he added, and the resulting guidelines underwent extensive internal and external review by other leading experts before further review by the ASCO board of directors and their own reviewers.

Their guideline recommendations included the following:

Patients with cancer who are hospitalized should be considered candidates for VTE prophylaxis with anticoagulants in the absence of bleeding or other contraindications to anticoagulation.

Routine prophylaxis with an antithrombotic agent is not recommended for ambulatory patients during systemic chemotherapy, but patients receiving thalidomide or lenalidomide with chemotherapy or dexamethasone are at high risk for thrombosis and warrant prophylaxis.

All patients undergoing major surgical intervention for malignant disease should be considered for thromboprophylaxis.

Low molecular weight heparin (LMWH) represents the preferred agent for both the initial and continuing treatment of patients with cancer who have established VTE.

The impact of anticoagulants on survival of patients with cancer requires additional study and cannot be recommended at present.

Patients with cancer should be encouraged to participate in clinical trials designed to evaluate anticoagulant therapy as an adjunct to standard anticancer therapies.

INNOHEP is indicated for the treatment of acute symptomatic deep vein thrombosis with or without pulmonary embolism when administered in conjunction with warfarin sodium. The safety and effectiveness of INNOHEP were established in hospitalized patients. It is an FDA approved indication.

:146–153).

The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 Suppl):627S-644S.
   
N.L. Rymes Outpatient management of DVT using low molecular weight heparin and a hospital outreach service Clinical & Laboratory Haematology Volume 24 Page 165  - June 2002 Volume 24 Issue 3

Richard Schreiber, Regarding clinical practice guidelines on the use of warfarin, Journal of the American Geriatrics Society Volume 49 Page 96  - January 2001 Volume 49 Issue 1

Highlights of the NCCN 11th Annual Conference: Clinical Practice Guidelines & Quality Cancer Care™, published as a supplement to The Oncology Report by Elsevier Oncology. © 2006 NCCN.

 

Home Prothrombin Testing

Lay Summary: Home Prothrombin testing is becoming standard in many countries, bit it is only now appearing in the USA. The literature shows that it is a relaible way of monitoring Coumadin therpay.

Near-patient testing (NPT) is becoming increasingly common in some countries. In the United Kingdom, for example, near-patient testing is used both by patients at home, and by some anticoagulation clinics (often hospital-based) as a fast and convenient alternative to the lab method. After a period of doubt about the accuracy of NPT results, a new generation of machines and reagents seems to gaining acceptance for its ability to deliver results close in accuracy to those of the lab.
In a typical NPT setup a small table-top device is used; for example the Roche Coagucheck® S, or the more recently (2005) introduced HemoSense INRatio®. A drop of capillary blood is obtained with an automated finger-#####, which is almost painless. This drop is placed on a disposable test strip with which the machine has been prepared. The resulting INR comes up on the display a few seconds later. Similar testing methods are used by diabetics on insulin, and are easily taught and practiced.

Local policy determines whether the patient or a coagulation specialist (nurse, general practitioner or hospital doctor) interprets the result and determines the dose of medication. In Germany, patients may adjust the medication dose themselves, while in the UK and the USA this remains in the hands of a health care professional.

The advantages of the NPT approach are obvious: it is fast and convenient, usually less painful, and offers, in home use, the ability for patients to measure their own INRs when required. Among its problems are that quite a steady hand is needed to deliver the blood to the exact spot, that some patients find the finger-######## difficult, and that the cost of the test strips must also be taken into account. In the UK these are available on prescription so that elderly and unwaged people will not pay for them and others will pay only a standard prescription charge, which at the moment represents only about 20% of the retail price of the strips. In the USA, NPT in the home is currently reimbursed by Medicare for patients with mechanical heart valves, while private insurers may cover for other indications.

There is some evidence to suggest that NPT may be less accurate for certain patients, for example those who have the lupus anticoagulant.

  1. Gardiner C, Williams K, Mackie IJ, et al. Patient self-testing is a reliable and acceptable alternative to laboratory INR monitoring. Br J Haematol. 2005;128(2):242-247.
  2. Fitzmaurice DA. Oral anticoagulation control: The European perspective. J Thromb Thrombolysis. 2006;21(1):95-100.
  3. Brown A, Wells P, Jaffey J, et al. Point-of-care monitoring devices for long-term oral anticoagulation therapy: Clinical and cost effectiveness. Technology Report No. 72. Ottawa, ON: Canadian Agency for Drugs and Technologies in Health (CADTH); February 2007. Available at: http://www.cadth.ca/index.php/en/hta/reports-publications/search/publication/679

Google Ads

Photo Albums

Google

  • Safe Search
    Google

Resources:

Categories