Low Molecular Weight Heparins
Cautions
- All the heparins may induce thrombocytopenia. Appearance of this adverse effect should be monitored by regular platelet counts. Treatment should be discontinued immediately if the patient presents a platelet count of under 100,000/mm3.
- Low molecular weight heparin (LMWH) should be administered with caution in the following situations:
- Severe hepatic failure
- Severe renal failure
- Uncontrolled arterial hypertension
- Hypertensive or diabetic retinopathy
Pharmacologic Interactions
LMWH should be administered with caution in patients who are treated with drugs that act on the hemostasis such as:
- Acetylsalicylic acid and other anti-platelet drugs
- Nonsteroidal anti-inflammatory drugs
- Oral anticoagulants
- Dextrans
- Thrombolytics
Adverse Reactions
Adverse reactions are more frequent with prolonged treatments over 3 months. The most characteristic adverse reactions are:
- Frequent (10–25%): hemorrhages and thrombocytopenia (within 1 to 20 days from the onset of treatment) that may be associated with thrombosis
- Occasional (1–9%): allergic disorders: pruritus, urticaria, asthma, rhinitis, fever, anaphylactoid reaction, allergic vasospastic reaction
- Rare (<1%): reaction in the site of injection, erythema, ecchymosis, bruising, cutaneous or subcutaneous necrosis
- Very rare (<1%): osteoporosis and bone fragility with high doses and in prolonged treatments (3 months or more)
Use In Pregnancy
Category B of the U.S. Food and Drug Administration (FDA). Heparins do not cross over the placental barrier. There can be increased risk of maternal hemorrhage when they are administered during the last weeks of pregnancy or in the post-partum period. With the efficacy and safety data available, they are recommended as first choice anticoagulant drug in pregnancy. The anti-factor X activity should be measured in pregnant women treated with LMWH at least once every three months, in order to maintain plasma activity levels between 0.25 and 0.35.
Oral Anticoagulants
Pharmacologic Interactions
Oral anticoagulants interact with multiple drugs. Special caution should be taken in the administration of analgesic and anti-inflammatory drugs, because the possibilities of interaction are numerous: displacement from plasma proteins, anti-platelet effect added to the anticoagulant one, or ulcerogenic effect that may become worse due to blood hypocoagulability.
Adverse Reactions
- Bleeding of different locations (gastrointestinal tract, brain, urogenital tract, uterus, liver, gall bladder, retroperitoneum, eyes, etc.) based on the intensity of the therapy, the age of the patient, and the nature of the baseline disease, but not on the duration of medication.
- Gastrointestinal discomfort (nausea, inappetence), allergic reactions in form of urticaria, dermatitis, and fever as well are irreversible loss of hair have rarely been described with coumarin derivatives.
- Some cases of haemorrhagic cutaneous necrosis generally related with congenital deficit of protein S and hepatic lesions have also been described.
Acetylsalicylic Acid
Pharmacologic Interactions
Acetylsalicylic acid strengthens the effect of acenocoumarol, warfarin, and heparin. The effect of ASA is inhibited by antacids and prednisone. The effect and toxicity of ASA are strengthened by cimetidine, ranitidine, and possibly dipyridamole.
Adverse Reactions
Very rare (<1%): nausea, dyspepsia, vomiting, gastric ulcer, duodenal ulcer, gastrointestinal hemorrhage (melena, hematemesis), urticaria, exanthematic eruptions, angioedema, rhinitis, serious paroxystic bronchial spasms, and dyspnea
Use In Pregnancy
Category C of the FDA. Sufficient studies do not exist to determine exactly the safety of the use of ASA at low doses during pregnancy. The use of this drug is only accepted if safer therapeutic alternatives are lacking.
