Anticoagulant management of pregnancy following heart valve replacement in the United Kingdom, 1986-2002.

BACKGROUND AND AIM OF THE STUDY: Patients with mechanical heart valves require anticoagulation which is associated with significant maternal mortality (1-4%) and fetal complications (31%) in pregnancy. The study aim was to identify anticoagulant protocols and outcomes for pregnant women undergoing heart valve replacement (HVR) in the United Kingdom. METHODS: Women aged between 18 and 45 years and registered with the United Kingdom Heart Valve Registry (UKHVR) each completed a questionnaire, and their obstetric notes were reviewed. The data analyzed included valve type (mechanical, bioprosthetic, homograft), valve site (mitral, aortic, tricuspid, pulmonary), anticoagulation at confirmation of pregnancy, between 6-12 weeks and from 12 weeks to term, delivery, maternal and fetal outcomes, and cause of death. The summary statistics and a descriptive review of the findings are reported. RESULTS: Of 2,532 women eligible for the study, 922 responded. Among these women, 72 became pregnant, with 60 pregnancies in the mechanical valve (MV) group and 45 in the tissue valve (TV) group. Three anticoagulation regimes were used during early pregnancy: unfractionated heparin (UFH), low-molecular-weight heparin (LMWH) or warfarin. All women received warfarin in the second trimester and heparin for delivery. Live births were recorded in 30% of MV pregnancies and in 60% of TV pregnancies. Miscarriage rates differed markedly (37% MV versus 2% TV). Fetal outcome was poorest in the warfarin-only group, with embryopathy occurring at a dose level of 6 mg. The maternal outcomes did not differ significantly among groups. High-dose heparin during the first trimester and for delivery was effective for the majority of mechanical valves. CONCLUSION: The study results illustrate the diverse and uncertain manner in which UKHVR patients are managed during pregnancy. A national notification system would record much-needed prospective information on anticoagulation and pregnancy outcomes, thus aiding evidence-based management.

Embolic complications of direct current cardioversion of atrial arrhythmias: association with low intensity of anticoagulation at the time of cardioversion.

OBJECTIVES: The goal of this study was to identify the factors responsible for embolic complications of direct current (DC) cardioversion of atrial arrhythmias. BACKGROUND: Direct current cardioversion of atrial fibrillation (AF) carries a risk of thromboembolism, which is reduced, but not eliminated, by anticoagulation. The risk of embolism after conversion of atrial flutter is believed to be lower. No series to date has included enough patients receiving anticoagulants or enough patients with atrial flutter to estimate the risk in these groups. METHODS: We reviewed the case records of 1,950 patients who underwent 2,639 attempts at DC cardioversion. RESULTS: Cardioversion was performed within two days of the apparent onset of the arrhythmia in 443 episodes, 352 without subsequent prolonged anticoagulation with one embolic complication. Cardioversion was preceded by warfarin therapy for > or = 3 weeks in 1,932 instances. No embolic complication occurred in 779 attempts performed with an international normalized ratio (INR) of > or = 2.5 (95% confidence limits 0% to 0.48%). Of 756 cases in which the INR was <2.5 or was not measured before conversion, nine were complicated by thromboembolism. Embolism was significantly more common at an INR of 1.5 to 2.4 than at an INR > or = 2.5 (0.93% vs. 0%, p = 0.012). The incidence of embolism after conversion of atrial flutter or tachycardia was similar to that after cardioversion of AF (0.72% vs. 0.46%, p = NS). CONCLUSIONS: The INR should be > or = 2.5 at the time of cardioversion if the duration of AF is uncertain or >2 days. Cardioversion of atrial flutter presents similar risks and requires similar anticoagulation.

Thrombopoietic agents.

Thrombopoietin (TPO) is the key cytokine involved in thrombopoiesis, and is the endogenous ligand for the thrombopoietin receptor that is expressed on the surface of platelets, megakaryocytes, and megakaryocytic precursors. First-generation thrombopoietic agents were recombinant forms of human TPO, and their development was discontinued after prolonged thrombocytopenia due to neutralizing auto-antibodies cross-reacting with endogenous TPO was observed. Second-generation thrombopoiesis-stimulating molecules are now available, which have unique pharmacological properties and no sequence homology to endogenous TPO. Two of these new agents, romiplostim and eltrombopag, have already completed phase III trials in primary immune thrombocytopenia and have been granted marketing authorization for use in this disease. Phase II and III trials with these novel drugs are ongoing in other conditions characterized by thrombocytopenia, such as chemotherapy, chronic liver disease, and the myelodysplastic syndromes. Most of the other second-generation thrombopoietic growth factors are in early phase clinical development.

Infectious causes of chronic immune thrombocytopenia.

Persistent thrombocytopenia may be the consequence of chronic infections with hepatitis C virus (HCV), human immunodeficiency virus (HIV), and Helicobacter pylori, and should be considered in the differential diagnosis of primary immune thrombocytopenia (ITP). Studies have shown that on diagnosis of infections, treatment of the primary disease often results in substantial improvement or complete recovery of the thrombocytopenia. In patients with thrombocytopenia due to HCV-related chronic liver disease, the use of eltrombopag, a thrombopoietin receptor agonist, normalizes platelet levels, thereby permitting the initiation of antiviral therapy. Antiviral therapy with highly active antiretroviral therapy for HIV has aided in platelet recovery, with a corresponding decrease in circulating viral load. Thrombocytopenia in the absence of other disease symptoms requires screening for H. pylori, especially in countries such as Japan, where there is a high prevalence of the disease and the chances of a platelet response to eradication therapy are high.

Pathobiology and treatment of hepatitis virus-related thrombocytopenia.

Thrombocytopenia is a well recognized complication of infections, including those from hepatotropic viruses. Thrombocytopenia may actually be the only manifestation of vital hepatitis, which should therefore be considered in the differential diagnosis of primary immune thrombocytopenia (ITP). The mechanisms of thrombocytopenia associated with viral hepatitis vary widely depending on the specific infectious agent and the severity of liver disease. Most of the studies have described thrombocytopenia in association with chronic hepatitis C virus (HCV) infection, the most common cause of chronic infection worldwide. Studies have shown that treatment of HCV infection often results in substantial improvement or complete recovery of the thrombocytopenia. In patients with thrombocytopenia associated with HCV-related chronic liver disease, the use of eltrombopag, a thrombopoietin receptor agonist, normalizes platelet levels thereby permitting the initiation of antiviral therapy.