Unfractionated heparin reverses aspirin inhibition of platelets during coronary artery bypass graft surgery.

Unfractionated heparin (UFH) is an effective antithrombotic during surgery but has known adverse effects, in particular on platelets. A marked increase in platelet responsiveness has previously been observed in patients within minutes of receiving UFH, despite adequate inhibition by aspirin prior to heparin. We studied this phenomenon in patients undergoing cardiac artery bypass grafting (n = 17) to determine whether the effects of heparin were systemic or platelet-specific. All patients' platelets were fully inhibited by aspirin prior to surgery, but within 3 min of receiving heparin spontaneous aggregation and responses to arachidonic acid (AA) and ADP increased significantly (p ≥ 0.0002), and activated platelets were found in the circulation. While there was no rise in thromboxane in the plasma following heparin, levels of the major platelet 12-lipoxygenase product, 12-HETE, rose significantly. Mixing experiments demonstrated that the changes caused by heparin resided primarily in the platelets, while addition of AA pathway inhibitors, and analysis of oxylipins provided evidence that, following heparin, aggregating platelets regained their ability to synthesise thromboxane. These findings highlight potentially unrecognised pro-thrombotic and pro-inflammatory changes during CABG surgery, and provide further evidence of adverse effects associated with UFH.

Hydroxyurea therapy: a rare cause of reversible azoospermia.

BACKGROUND: Essential thrombocythaemia (ET) is an uncommon chronic myeloproliferative disorder characterized by a marked increase in the number of platelets. Hydroxyurea is effective in preventing thrombosis in high-risk patients with essential thrombocythaemia. In previous studies different side effects of Hydroxyurea have been pointed out, but attention has not really been focused on the possible side effects on spermatogenesis. CASE: A 35-year-old man under investigation for haematospermia and complaining of erythromyalgia was found to have a thrombocytosis with a platelet count of 1130 x 10(9)/l. Bone marrow aspiration confirmed a diagnosis of essential thrombocythaemia. He was commenced on hydroxyurea (2 g daily) in order to lower his platelet count and relieve the erythromyalgia. The patient represented to the urologists, 3 years later with infertility and a semen analysis done by his doctor had shown azoospermia. Monthly sperm counts after the withdrawal of hydroxyurea showed a gradual return of the spermatogenesis to normal over a period of around 6 months. The patient's wife had conceived within 4 months of him stopping hydroxyurea. CONCLUSION: This case highlights a very rare but nonetheless important side effect of treatment with hydroxyurea. Hydroxyurea can cause reversible inhibition of spermatogenesis and result in primary infertility. We believe that all patients being commenced on such treatment should be warned of this possibility and that they should be given the necessary follow-up investigations.