Pregnancy-specific reference ranges for haematological variables in a Scottish population.

Using laboratory reference ranges, B12 deficiency is inappropriately diagnosed and treated in pregnancy. We aim to define reference ranges for ferritin, folate, haemoglobin and B12 in a pregnant population with advancing gestation. A total of 190 women participated in a cross-sectional study, 113 in the 1st and 77 in the 3rd trimester. All variables studied except red cell folate, decreased significantly from the 1st to the 3rd trimester. A total of 34% (64/190) of women were found to have 'low' B12 as defined by traditional ranges. In women with anaemia and apparent B12 deficiency, co-existing ferritin deficiency was demonstrated. All women with 'low' B12 levels were invited to attend postnatally for re-testing. A total of 28% (18/64) attended, in whom all B12 levels spontaneously increased. The use of gestation specific reference ranges for haematological variables may reduce inappropriate diagnosis of B12 deficiency. In most women with apparent low B12 levels and anaemia, ferritin deficiency was demonstrated. Therefore iron should be the initial management therapy.

Risk factors for pregnancy associated venous thromboembolism.

In an attempt to reduce the incidence of pregnancy associated venous thromboembolism (PA-VTE), some researchers have advocated screening of all women for the factor V(Leiden) mutation during early pregnancy. We have conducted a large retrospective study (over 72,000 deliveries) to determine if this would be useful. Sixty-two objectively confirmed venous thrombotic events (51 DVT, 11 PE) were recorded at two maternity units in the UK. The incidence of DVT was 0.71 per 1000 deliveries (95% CI 0.5-0.9) with 0.50 occurring in the antenatal period (95% CI 0.34-0.66) and 0.21 in the puerperium (95% CI 0.11-0.31). The incidence of PE was 0.15 per 1000 deliveries (95% CI 0.06-0.24), 0.07 antenatal (95% CI 0.01-0.13) and 0.08 in the puerperium (95% CI 0.02-0.14). Of these 62, 50 attended for follow-up and thrombophilia screening. 28% of all episodes of PA-VTE had no clinical risk factor for thrombosis or an identifiable thrombophilic abnormality. Deficiency of antithrombin was identified in 12% of individuals (95% CI 3-21) and the factor V(Leiden) mutation in 8% (95% CI 0.5-15.5). Based on estimates of the prevalence of the factor V(Leiden) mutation in the population, we estimate that the thrombotic risk for a woman during pregnancy or the puerperium with the defect is approximately 1 in 400-500. This figure would not lend support to the idea of random screening for the mutation in early pregnancy.

Factor V Leiden, prothrombin 20210G-->A and the MTHFR C677T mutations in childhood stroke.

Ischaemic stroke is a rare occurrence in children and in a proportion of cases the aetiology remains unknown. We have investigated the role of thrombophilia in the aetiology of this condition. Of 50 cases identified at two centres, 37 were available for detailed haematological analysis. No cases were identified with deficiencies of antithrombin, protein C or protein S. One case had elevated IgG anticardiolipin antibodies at low titre. The prevalence of the prothrombin 20210 G-->A mutation, factor V Leiden (FVL) mutation and the C677T mutation in the MTHFR gene was compared in cases to that observed in random unselected cord blood controls. The odds ratio for stroke was not significantly increased in carriers of the prothrombin mutation (OR 1.2; 95% CI 0.1-10.7), FVL (OR 2.5; 95% CI 0.5-13.5), or the C677T mutation (OR 1.7; 95% CI 0.6-4.5). Our findings suggest that thrombophilia may not play a significant role in the aetiology of stroke in children, although a large prospective study is required to investigate this area further.

Superficial vein thrombosis: incidence in association with pregnancy and prevalence of thrombophilic defects.

Superficial venous thrombotic (SVT) events are a feature of thrombophilic abnormalities, particularly those involving the protein C pathway. We have determined the incidence of SVT associated with pregnancy and the early postpartum period in a retrospective study involving 72000 deliveries. Fourty-nine cases occurring in 47 individuals were recorded, with an overall incidence of 0.68/1000 deliveries (95% CI 0.48-0.88). None had a previous history of deep vein thrombosis or pulmonary embolism. Most events occurred in the early postpartum period (0.54/1000 deliveries). Twenty-four/fourty-seven were screened for established thrombophilic abnormalities, with only 1 abnormality detected (FV(Leiden) heterozygote). Thrombophilia may play a minor role in the aetiology of SVT associated with pregnancy, although a larger study is required to confirm this.

Respiratory syncytial virus infection in adult BMT recipients: effective therapy with short duration nebulised ribavirin.

Respiratory syncytial virus (RSV), a common cause of both upper and lower respiratory tract infection (LRTI) in infants and children, is rarely described as an infective agent in adults. It has been reported in bone marrow transplant (BMT) recipients and patients with malignancy immunosuppressed by chemotherapy. Such reports are often associated with a high mortality. We report an outbreak of RSV infection which occurred predominantly in BMT recipients in which early investigation and institution of ribavirin therapy resulted in all patients making a full recovery.

The role of hepatitis C virus in the aetiology of non-Hodgkins lymphoma--a regional association?

Infection with the Hepatitis C virus (HCV) has been aetiologically linked with the lymphoproliferative disorder mixed cryoglobulinaemia and more recently with certain subgroups of B cell non-Hodgkin's lymphoma (NHL). Many of the studies which have documented the association with NHL have originated from Italy, where the background prevalence of infection with the virus is relatively high. We have performed a study, based in the West of Scotland, to determine the prevalence of infection with HCV in an unselected group of 110 individuals with lymphoproliferative disorders (72 with NHL, and 38 with chronic lymphocytic leukaemia). None of our cohort (both NHL and CLL) had evidence of infection with the virus. Our study suggests that whilst HCV may be important in the aetiology of certain subgroups of NHL, this effect may be regional and dependent upon the background prevalence of the virus in the community.

Reversal of nonarteritic anterior ischemic optic neuropathy associated with coexisting primary antiphospholipid syndrome and Factor V Leiden mutation.

PURPOSE: To report nonarteric anterior ischemic optic neuropathy (NAION) as an ocular manifestation in a woman with combined primary antiphospholipid syndrome and Factor V Leiden (FVL) mutation. METHODS: Case report of a middle-aged woman with hematological investigations confirming the diagnosis of both primary antiphospholipid syndrome and Factor V Leiden mutation, who presented with visual disturbance in her left eye. RESULTS: NAION was noted in her left eye. The patient was promptly treated with low molecular weight heparin, followed by warfarin, which resulted in the reversal of the ischemic optic neuropathy. CONCLUSIONS: Primary antiphospholipid syndrome and coexisting Factor V Leiden mutation should be considered in the differential diagnosis of NAION. Prompt treatment with anticoagulants can result in the reversal of the ischemic process.

Management of heparin allergy during pregnancy with danaparoid.

We report a patient who presented with a left proximal deep vein thrombosis at 25 + 5 weeks gestation. She developed a severe urticarial rash 3 weeks following initiation of therapy with Enoxaparin. The patient was heterozygous for the factor V Leiden mutation. She was treated with subcutaneous twice-daily danaparoid (Orgaran) for the remainder of the pregnancy, achieving anti-Xa levels in the therapeutic range 0.5-1.0 IU/ml. Delivery was at term by caesarean section 2 days after spontaneous rupture of membranes and failure to progress in labour. Danaparoid was withheld during this time. Danaparoid was restarted 3 h post delivery and the patient anticoagulated with warfarin in the post-partum period. There was no recurrence of thrombosis or bleeding events during therapy with danaparoid. No anti-Xa activity was demonstrated in breast milk.

Asymptomatic coinheritance of heterozygous plasminogen deficiency and the factor VLeiden mutation.

Deficiency of plasminogen has been postulated by some authors as a possible thrombophilic abnormality, though this remains controversial. We have previously identified a cohort of individuals with plasminogen deficiency from a study to determine plasminogen levels within the general population. All were asymptomatic for thrombosis at initial identification. We followed this cohort over a 5-year period, with no venous thrombotic events recorded, although one patient did suffer a myocardial infarction. One family was identified with asymptomatic coinheritance of both plasminogen deficiency and the factor VLeiden mutation. There was no apparent venous thrombotic risk conferred upon any of our cohort of individuals by inheritance of plasminogen deficiency, and, in addition, the combination of the factor VLeiden mutation with plasminogen deficiency which was observed in three individuals did not result in thrombotic events. However, the cohort is small and we cannot entirely exclude plasminogen deficiency as a possible mild thrombophilic defect.

Lipoprotein (a), cholesterol and triglycerides in women with venous thromboembolism.

Plasma concentrations of lipoprotein (a), total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglyceride were measured in 62 women who had suffered an episode of objectively confirmed venous thromboembolism (VTE) at < or = 50 years of age, and in 98 age-matched female controls. The mean body mass index (BMI) of cases was significantly (P < 0.001) higher than that of controls. Plasma triglyceride was significantly higher, and total cholesterol/LDL- and HDL-cholesterol significantly lower, in cases compared with controls. After adjustment for BMI, the plasma total cholesterol and LDL-cholesterol remained significantly lower in cases. No significant differences in mean plasma lipoprotein (a) levels were identified between cases and controls. Lipoprotein (a) does not appear to be significantly associated with the development of VTE in young women. The increased risk of VTE in obese subjects may be mediated, at least in part, via hypertriglyceridaemia, which has previously been demonstrated to have effects on levels of coagulation factors, natural anticoagulants, and plasminogen activator inhibitor type 1.

Low-molecular-weight heparin for the prevention and treatment of venous thromboembolism in pregnancy.

PURPOSE OF REVIEW: Low-molecular-weight heparins (LMWHs) have largely replaced unfractionated heparins for both prophylaxis and treatment of venous thromboembolism in nonpregnant patients. However, until recently, evidence in pregnant women was lacking, despite the increasing use of LMWHs during pregnancy in clinical practice. This review covers recent literature on the use of LMWHs in relation to pregnancy. RECENT FINDINGS: The main areas covered in this review are the use of LMWHs in both prophylaxis and treatment of venous thromboembolism in pregnancy. The review also considers issues relating to monitoring of LMWHs in pregnancy, and safety from both a maternal and a fetal perspective. SUMMARY: The available evidence demonstrates that LMWHs are of at least equivalent efficacy but have a better safety profile compared with unfractionated heparins in both prophylaxis and treatment of maternal venous thromboembolism, and are more convenient to administer. There is no consensus with respect to whether these agents require monitoring during pregnancy other than periodic checking of the platelet count. The clinical implication from the available evidence is that LMWHs should now be regarded as the anticoagulant agents of choice for both prophylaxis and treatment of maternal venous thromboembolism.

Sibling allogeneic bone marrow transplantation in a patient with type I Glanzmann's thrombasthenia.

Glanzmann's thrombasthenia is a rare inherited bleeding disorder caused by either quantitative or qualitative abnormalities of the platelet membrane glycoprotein (Gp) IIb/IIIa complex. Bleeding is usually mucocutaneous in origin and may be of a severe nature. We report the use of allegeneic bone marrow transplantation in a 5-year-old child with homozygous type I Glanzmann's thrombasthenia, using the patient's younger brother as marrow donor. Engraftment was successful and has resulted in a resolution of bleeding episodes. We conclude that allogeneic BMT is a potentially curative option for those with Glanzmann's thrombasthenia associated with severe bleeding symptoms.

The role of inherited thrombophilia in venous thromboembolism associated with pregnancy.

Venous thromboembolism is an important cause of maternal morbidity and mortality. The puerperium should be regarded as the period of greatest risk. However, fatalities in early pregnancy emphasise the need to assess thrombotic risk at all stages of pregnancy. In many cases those at increased risk are potentially identifiable on clinical grounds alone such as those with a personal or family history of venous thromboembolism, obesity, or surgery. Identification of women with multiple clinical risks for thrombosis during pregnancy remains the key to reducing the incidence of this condition. In women who present with a personal or family history of proven venous thromboembolism, thrombophilia screening should be performed in early pregnancy, since the results may influence subsequent management during pregnancy. The investigation and management of patients considered at increased risk of venous thrombosis during pregnancy requires close liaison between obstetricians and haematologists familiar with this rapidly expanding and complex field of thrombophilia.

Risk factors for venous thromboembolism in pregnancy.

Venous thromboembolism remains the leading cause of maternal mortality in the United Kingdom. In this review we highlight studies that have documented the incidence of objectively confirmed venous thromboembolism in pregnancy, consider the effect of pregnancy on the coagulation and fibrinolytic systems, and examine in detail current knowledge of the risk factors for the development of this condition.

Prevalence of the post-thrombotic syndrome in young women with previous venous thromboembolism.

The prevalence of mild, moderate and severe post-thrombotic syndrome (PTS) among 43 young women with a previous single episode of deep vein thrombosis (DVT) was 67%, 7% and 0% respectively. Subjects were assessed at a mean 51 months after the event. Moderate PTS was more common in women with recurrent (n = 9) DVT (44%, P < 0.001). Chronic venous insufficiency, assessed by light reflection rheography (LRR), was significantly (P < 0.05) more prevalent in women with single previous DVT (n = 40), recurrent DVT (n = 9) and isolated pulmonary embolism (PE) (n = 19) compared with healthy age-matched controls (odds ratios 10.9, 52.4 and 3.8 respectively). LRR findings correlated with moderate, but not mild, PTS. There was no correlation between development of PTS and body mass index.

Acute renal failure complicating high-dose intravenous immunoglobulin therapy for acquired haemophilia.

Acquired haemophilia is a rare disorder requiring therapy to control bleeding and to suppress the inhibitory antibody. High-dose intravenous immunoglobulin is commonly used as part of immunosuppressive regimens for this condition. We describe the case of an elderly patient who developed acute oliguric renal failure as a result of intravenous immunoglobulin therapy. All patients receiving such treatment should have renal function carefully monitored both during and after the infusion.

Injecting drug use is a risk factor for deep vein thrombosis in women in Glasgow.

Three hundred and twenty-two consecutive women aged 16-70 years who presented with objectively confirmed symptomatic venous thromboembolism (VTE) were studied to determine precipitating factors for thrombosis. One hundred and eighty-seven presented with deep vein thrombosis (DVT), 116 with either definite or possible pulmonary embolism (PE) and 19 with both DVT and PE. Injecting drug use (IDU) via femoral vein puncture was a common risk factor for DVT, associated with 21.4% of all cases of DVT and 52.4% of cases of DVT in women under 40 years. All women with drug-related thrombosis presented with DVT. None presented with symptomatic PE. A number of clinically diagnosed DVT associated with IDU were also documented, suggesting that IDU may be the most common risk factor for DVT in our region. DVT associated with IDU presents significant management challenges.

Prothrombin 20210 G-->A, MTHFR C677T mutations in women with venous thromboembolism associated with pregnancy.

Over 50 unselected women with maternal venous thromboembolism were screened for the prothrombin 20210 G-->A and MTHFR C677T mutations, in addition to screening for other thrombophilias. The prevalence of thrombophilia in these women was compared with its prevalence in the general population in our area. The prothrombin (OR 4.4; 95% CI 1.2-16) and factor V Leiden (OR 4.5; 95% CI 2.1-14.5) mutations were more common in our patients, compared with the general population, whereas women homozygous for the C677T mutation in the methylene tetrahydrofolate reductase gene (OR 0.45; 95% CI 0.13-1.58) were not. It is recommended that women with a personal or strong family history of venous thromboembolism should be screened for the prothrombin mutation either before or early in pregnancy, in addition to screening for other thrombophilias. Screening for the MTHFR mutation does not appear to identify women at increased risk of maternal venous thrombosis.