Primary atherothrombotic occlusive vascular events in premenopausal women with history of adverse pregnancy outcome.

OBJECTIVE: To determine if adverse pregnancy outcomes are associated with atherothrombotic occlusive vascular disease (AOVD) in premenopausal women. DESIGN: Retrospective matched case-control study. SETTING: Tertiary, university-affiliated medical center. POPULATION: Women aged less than 50 years treated for an AOVD (primary cerebrovascular, myocardial, or peripheral arterial ischemic event) from 1995 to 2004. METHOD: The files were reviewed for classical risk factors for AOVD and complications of pregnancy (abortions, pregnancy-induced hypertension, preeclampsia, gestational diabetes, intrauterine growth restriction (IUGR), fetal loss and preterm delivery). Findings were compared with healthy women matched for age and body mass index. MAIN OUTCOME MEASURES: Past pregnancy complications in premenopausal women with AOVD. RESULTS: Of the 101 women with AOVD, 53 had a myocardial ischemic event, 33 a cerebrovascular event, and 15 a peripheral ischemic arterial event. On multivariate analysis, IUGR (OR 8.41, 95% CI 2.36-29.9, p=0.001) and more than one pregnancy complication (OR 13.7, 95% CI 1.56-120, p=0.02) were found to be independent significant variables associated with AOVD. CONCLUSION: IUGR and composite pregnancy complications are independent significant variables associated with AOVD in premenopausal period. Pregnancy outcome might serve as a means to identify patients who may require increased medical surveillance and preventive measures for later vascular disease.

Non-Hodgkin's lymphoma in patients 80 years of age or older.

BACKGROUND: Very elderly patients (> or =80 years old) with non-Hodgkin's lymphoma (NHL) frequently have co-morbid conditions and are generally excluded from clinical trials or even from treatment. The optimal treatment of these patients is unknown. PATIENTS AND METHODS: We reviewed the records of 109 patients > or =80 years at diagnosis of NHL (65 F/44 M; median age: 84 years, range; 80-95). RESULTS: Seventy-eight patients (72%) had aggressive NHL, 25 (23%) had indolent and NHL, eight had unclassified disease. Advanced-stage disease was noted in 54%. Forty patients (39%) had a poor ECOG performance status (PS), and 52 (49%) had an intermediate or high risk International Prognostic Index (IPI). Seventy-nine patients (72%) were treated with chemotherapy and 37 (34%) with radiotherapy. Initial chemotherapy consisted of chlorambucil in 15, oral etoposide in 2, and combination protocol in 62. Only 16% of patients received full-dose therapy, and only 50% completed > or =6 cycles of combination chemotherapy. The overall response rate for the 69 evaluable patients was 84% (complete 56.5%, partial 27.5%). Overall 5-year survival for the whole group was 39%, and median survival time was 26 months. CONCLUSION: A high response rate can be achieved in very elderly NHL patients despite aggressive histology, poor prognostic features, and reduced doses of chemotherapy. Age alone should not be a contraindication to treatment.

Retrospective analysis of the use of inferior vena cava filters in routine hospital practice.

INTRODUCTION: Characteristics and outcomes of patients undergoing inferior vena cava (IVC) filter insertion are not well reported. Particularly, the role of long term anticoagulation in these patients is unclear. AIMS: (1) To describe in a cohort of patients undergoing IVC filter insertion, underlying diseases, indications for filter insertion, complications, and survival. (2) To determine the effect of long term anticoagulant treatment on thromboembolism and patient survival. STUDY DESIGN: A retrospective analysis of 109 consecutive patients undergoing IVC filter insertion in two university hospitals. RESULTS: Average age was 67.4 years. Median duration of follow up was two years. Indications for IVC filter insertion were: contraindication to anticoagulation (n = 61, 56%), prophylactic insertion (n = 29, 27%), thromboembolism while receiving adequate anticoagulation (n = 17, 15%), and non-compliance with anticoagulation (n = 2, 2%). Insertion related complications were groin haematoma in four patients (3.5%) and localised infection at the puncture site in one patient (0.9%). Fifty six patients (51.4%) died during the study period. Of these, 22 received long term anticoagulants and 34 did not. Overall and thrombosis free survival was greater in the anticoagulant treated group (median survival not reached) than in the untreated group (median survival = 12 months). Patients not receiving long term anticoagulation after IVC filter insertion were nearly 2.5-fold more likely to die or experience venous thromboembolism. CONCLUSION: IVC filter insertion was a safe procedure and was performed for appropriate indications in the patients studied. In patients surviving for longer than 30 days, prolonged administration of oral anticoagulants was associated with improved survival with no significant increase in haemorrhagic complications.

A case of cellulitis complicating Campylobacter jejuni subspecies jejuni bacteremia and review of the literature.

Infection with Campylobacter species is a predominant cause of food-borne gastroenteritis in the industrialized world. Bacteremia is detected in <1% of patients with diarrhea, mainly in immunocompromised hosts or those in the extremes of age. Reported here is the case of a 78-year-old, immunocompromised male patient with Campylobacter jejuni subsp. jejuni bacteremia complicated by cellulitis. The infection was characterized by a protracted course with several recurrences and refractoriness to multiple antibiotic regimens, responding only to a prolonged course of meropenem treatment. The frequency of cellulitis as reflected in previously reported series of Campylobacter bacteremia and the clinical characteristics of this difficult-to-treat infection are reviewed.

The risk of fetal loss associated with Warfarin anticoagulation.

OBJECTIVES: To examine if fetal risks associated with Warfarin anticoagulation during pregnancy may have been over-estimated at the time the drug was contraindicated during pregnancy. METHODS: Seven case series with the same therapeutic objective for Warfarin anticoagulation published after 1980 were identified. The frequencies of fetal complications were calculated and compared with those of the 1980 compilation. RESULTS: The frequencies of embryopathy, stillbirths, and neonatal deaths were similar to the 1980 database, but higher with respect to spontaneous abortions (24.1 vs. 8.6%) and premature deliveries (13.9 vs. 4.6%), and lower regarding live births (73.3 vs. 83.7%). CONCLUSIONS: Fetal risks associated with Warfarin anticoagulation during pregnancy have not been overestimated. Warfarin should not be given in cases where other anticoagulants do not increase the risk for the expecting mother.

Primary lymphoma of the breast: unusual presentation of breast cancer.

OBJECTIVE: To investigate 4 cases of primary lymphoma of the breast and review previous studies in a search for any preoperative characteristics that could assist the diagnosis of lymphoma of the breast. DESIGN: Retrospective study. SETTING: University hospital, Israel. SUBJECTS: 4 women. MAIN OUTCOME MEASURES: Accurate diagnosis before operation. RESULTS: No special characteristics for early diagnosis of primary malignant lymphoma of the breast were found. The predominant involvement of right breast in primary lymphoma of the breast should be noted. CONCLUSIONS: Even though primary lymphoma of the breast is rare, there are no laboratory or imaging signs of early diagnosis. Excisional biopsy or Tru-cut biopsy are the only correct methods of diagnosis.

Increased D-dimer levels in twin gestation.

In normal pregnancy, the hemostatic balance is displaced toward hypercoagulability. The elevation in plasma levels of coagulation factors VII, VIII, and X and fibrinogen and the increased concentrations of plasminogen activator inhibitors [1,2] may predispose individuals to thromboembolism, especially near term [1,3]. Because human multifetal gestation requires still greater physiological alterations, the imbalance in hemostasis is further exaggerated. It has been suggested that the changes in the coagulation system near term may even mimic low-grade disseminated intravascular coagulopathy [4]. However, for the majority of women with multifetal gestation, the coagulopathy observed in the laboratory is not clinically apparent [5]. Despite the large body of research on the physiological adaptation to pregnancy, relatively little is known of the biological adaptation in general and the hemostatic changes in particular associated with multiple gestation.

Low-molecular-weight heparin for thrombophilia in pregnant women.

OBJECTIVE: Low-molecular-weight heparin (LMWH) is the anticoagulant of choice during pregnancy because it is associated with a low incidence of osteoporosis and thrombocytopenia. Antithrombotic therapy has recently been used to prevent pregnancy loss in high-risk patients with evidence of acquired or congenital thrombophilia. The aim of the present study was to gain further information on the teratogenic potential of LMWH in this patient group. METHODS: The study population included 46 patients with a history of recurrent abortions, intrauterine fetal death or intrauterine growth restriction (IUGR) and severe early-onset preeclampsia. Patients with a history of thromboembolism or positive findings for thrombophilia were prescribed LMWH (enoxaparin sodium, 40 mg daily) in combination with low-dose aspirin (100 mg daily) in the first trimester (group 1, n=14) or the second trimester (group 2, n=17); the remaining 15 patients received low-dose aspirin alone (group 3). RESULTS: No significant differences were noted between the groups in the incidence of congenital malformations or abortions, IUGR or preterm deliveries. One infant in group 1 had familial bilateral postaxial polydactyly of the hands and one in group 3 had patent ductus arteriosus. CONCLUSION: Despite the small size of the study groups, our results support the assumption that the use of LMWH is safe, at least as a teratogenic agent, in patients with thrombophilia throughout pregnancy.

Unilateral vocal cord paralysis as a result of a Nocardia farcinica laryngeal abscess.

Nocardia farcinica is an emerging pathogen in immunocompromised hosts, accounting for 20% of Nocardia isolates in the USA and 13-44% of isolates in Europe. The case of a 72-year-old lymphoma patient with a laryngeal abscess caused by Nocardia farcinica is presented. The initial clinical manifestation was unilateral vocal cord paralysis, which improved following surgical drainage of the abscess and therapy with imipenem. The English-language literature on human Nocardia farcinica infection is reviewed.

Cutaneous necrosis as a terminal paraneoplastic thromboembolic event in a patient with non-Hodgkin's lymphoma.

Thrombotic complications in non-Hodgkin's lymphoma often originate in the large veins. We describe a patient with refractory advanced high-grade lymphoma who presented with the rare complication of extensive cutaneous necrosis due to thrombosis of dermal vessels; there was also a recent new peak of monoclonal IgM-kappa protein. Direct immunofluorescence demonstrated immune deposits with complement in the dermal vessel wall. Based on these observations and on published data, we suggest that these complexes were the trigger for the thrombotic events and that the monoclonal IgM acted as xenoreactive antibodies, initiating a cascade of events. The first step of this cascade was activation of the complement and the membrane attack complex, which caused secretion of IL-1 alpha by endothelial cells, followed by overexpression of tissue factor on the surface of the dermal vessel wall endothelium. Dermal vessel thrombosis was the final event in this cascade.

Significance of BCR-ABL transcripts in bone marrow aspirates of Philadelphia-negative essential thrombocythemia patients.

Philadelphia-negative (Ph-neg) essential thrombocythemia (ET), polycythemia vera (PV) and idiopathic myelofibrosis (IMF) form a syndrome of related chronic myeloproliferative disorders (MPD) characterized by expansion of one or more of the hematopoietic progenitors. Based on our previous finding of BCR-ABL transcripts in bone marrow aspirates of 12/25 Ph-neg ET patients, we have expanded our study up to 40 patients. Here we describe the rational for performing this study and report 19 of 40 patients who have BCR-ABL transcripts in their BM, 11 of them carry b3a2 and 8 carry b2a2. The two groups, BCR-ABL positive and negative, were completely identical with regard to clinical characteristics and laboratory data. We also report preliminary results of our attempt to examine concordance or discordance of BCR-ABL expression in the peripheral blood and bone marrow of Ph-neg ET patients.

Red blood cell zinc protoporphyrin measurement for assessment of peripartum iron deficiency.

OBJECTIVE: To study the effectiveness of the rapid red blood cell zinc protorphyrin (RBC-ZPP) test for the detection of women with iron-deficiency anemia in the peripartum period. DESIGN: Blood was drawn prospectively from 150 healthy parturient women upon admission to the labor and delivery room and 72 hours after delivery. Concentration of RBC-ZPP was measured and correlated with hemoglobin level (p = 0.001), mean corpuscular volume (p = 0.002), hematocrit (p = 0.0001), platelet count (p = 0.002), and serum iron (p = 0.0001), serum ferritin (p = 0.0001) and serum transferrin (p = 0.0001) concentrations. RESULTS: RBC-ZPP concentration showed a significant increase from pre-delivery to 72 hours post-delivery. This change correlated significantly with the changes in all the other parameters studied. CONCLUSION: The RBC-ZPP test is a reliable, rapid, easy-to-perform, and inexpensive method of screening low-risk women, after uneventful vaginal delivery, for iron deficiency.

Pleural effusion in patients with non-Hodgkin's lymphoma: a case-controlled study.

BACKGROUND: Pleural effusion is reported in up to 20% of patients with non-Hodgkin's lymphoma (NHL), most often at presentation. However, the prognostic implications of such findings are not clear. The majority of the information in the literature is based on minor observational studies or case reports. Therefore, a case-controlled study was performed to verify the clinical significance of pleural effusion in NHL. METHODS: Seventeen patients with pleural effusion at the time of presentation of NHL were identified. They were categorized by grade of NHL (based on the Working Formulation). Twenty-nine control patients with similar histopathologic characteristics who had Stage III/IV NHL without pleural effusion were matched to these cases by age, time of diagnosis, and treatment. RESULTS: Ten patients with intermediate grade NHL were matched with 23 controls. No statistically significant difference in complete remission or survival rates between these groups was found (P=0.69 and P=0.7, respectively). The remission and survival rates also were similar in the subgroup of patients and controls who were treated with aggressive chemotherapy. Similarly, no difference was found in these parameters between four cases and six matched controls with low grade lymphoma. No matched controls were found for the patients with high grade lymphoma, but these patients had an unfavorable outcome. Fourteen of the 17 studied patients had an exudative type of pleural effusion. Thoracentesis yielded a positive cytologic finding in every case. CONCLUSIONS: The presence of pleural effusion at the time of presentation of NHL does not adversely affect complete remission or survival rates.

BCR-ABL transcripts in bone marrow aspirates of Philadelphia-negative essential thrombocytopenia patients: clinical presentation.

One of the diagnostic criteria of essential thrombocythemia (ET) is the absence of the Philadelphia chromosome (Ph-neg). On the molecular level, Ph-neg ET patients may carry BCR-ABL transcript. The natural history of BCR-ABL positive Ph-neg ET patients is undetermined. We examined the BCR-ABL status by reverse transcriptase two-step nested polymerase chain reaction in bone marrow aspirates of 25 Ph-neg ET patients. We found 12 BCR-ABL positive and 13 BCR-ABL negative patients in the study group. The comparison showed that the two groups had similar clinical and laboratory characteristics, except for a significant increased patients' age and decreased polymorphonuclear cell count in the BCR-ABL positive group. During a median follow-up of 20 and 22.5 months for the BCR-ABL negative and positive groups, respectively, there was neither blastic transformation nor unrelated death in both groups. We conclude that it is important to look for BCR-ABL transcript in Ph-neg ET patients and to follow them closely to investigate the nature of this translocation in this group of patients.

Thrombotic complications in essential thrombocythemia with relatively low platelet counts.

Essential thrombocythemia (ET) is often associated with thrombotic and hemorrhagic complications, mostly at platelet counts exceeding 600 x 10(9)/L. There are, however, a few reports of such complications in ET at considerably lower platelet levels and the therapeutic approach to affected patients with relatively low platelet counts is still controversial. In the present study, the first to directly address the issue of hemostatic manifestations at relatively low platelet counts, we have determined the lowest platelet counts associated with such manifestations in 56 consecutive ET patients. Clinical manifestations related to ET were recorded in 46 (82%) patients. Of the symptomatic patients, 32 (70%) had symptoms at platelet counts lower than 600 x 10(9)/L, 23 (50%) at counts lower than 500 x 10(9)/L, 10 (22%) at counts lower than 400 x 10(9)/L, and 6 patients (13%) at platelet counts as low as 300-350 x 10(9)/L. Severe complications occurred at platelet counts lower than 600 x 10(9)/L in 10 patients (22%), lower than 500 x 10(9)/L in 7 (15%), and at lower than 400 x 10(9)/L in 2 (4%). Thrombotic neurologic symptoms were the most common (31 patients, 67%), followed by peripheral vascular symptoms (17 patients, 37%); hemorrhagic complications were relatively rare (3 patients, 7%). In most cases, cessation or improvement of clinical manifestations was observed only after further reduction in platelet counts. In conclusion, thrombotic manifestations, including severe ones, are not uncommon in ET at relatively low platelet counts. We recommend that symptomatic patients with relatively low platelet counts be treated and the platelet counts further reduced well into the lower normal range.

Levels of proteins C and S do not decline subsequent to first line chemotherapy in lymphoma patients.

Thromboembolic complications and decrease in protein C and S have been observed in patients while receiving combination chemotherapy for breast cancer. We investigated whether initial cytotoxic treatment of non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) is also associated with changes in these anticoagulant parameters. For this purpose 25 patients with intermediate to high grade NHL and seven with HD, undergoing primary treatment with cytotoxic drugs were evaluated at three time-points: pre-therapy, mid-therapy and post-therapy. In contrast to the breast cancer patients, no significant changes in protein C, protein S and antithrombin III levels were observed in the NHL patients during the various stages of therapy. However in HD patients, the mean protein C values had a tendency to be higher at mid-therapy compared to pre-therapy and protein S levels had a tendency to be higher at mid-therapy compared to post-therapy. In lymphoma patients receiving primary cytotoxic treatment we did not find changes in anticoagulant parameters that can explain a chemotherapy-induced hypercoagulable state, as has been reported in breast cancer patients.

Severe myelotoxicity of oral etoposide in heavily pretreated patients with non-Hodgkin's lymphoma or chronic lymphatic leukemia.

BACKGROUND: Promising results have been reported for patients with non-Hodgkin's lymphoma (NHL) receiving chronic oral etoposide. Due to the small number of patients reported, information regarding side effects is limited, and therefore warrants further evaluation. METHODS: Twenty eligible patients with NHL and chronic lymphatic leukemia (CLL), resistant to or relapsed after previous protocols of polychemotherapy were treated with oral etoposide at a dosage of 50 mg/m2/day for 21 days in a 28-day cycle. Response and toxicity were evaluated according to standard criteria. RESULTS: Total response was noted in 13 patients, complete response in 2 patients, and partial response in 11 patients. Two patients had stable disease and five patients had progression of disease during treatment. Seventy-five percent of patients experienced neutropenia below 1500/microL. Half acquired infection and required hospitalization. Fifty-five percent required blood transfusions. All patients needed course shortening and dosage reduction. CONCLUSIONS: Chronic daily administration of oral etoposide is effective in patients with NHL and CLL. In heavily pretreated patients, myelotoxicity is severe. Therefore, modification of the schedule plan is mandatory in this group of patients.

Evaluation of solvent/detergent treated plasma in the management of patients with hereditary and acquired coagulation disorders.

Haemostatic efficacy and pharmacokinetic analysis of solvent/detergent (S/D) treated, virus inactivated plasma (Octaplas, Germany) was evaluated in eight patients with hereditary factor VII, X and XI deficiency and in three patients with acquired coagulation disorders due to liver disease. The patients received the S/D plasma for treatment of haemarthrosis, menorrhagia or before surgical procedures. In all the patients the S/D plasma was sufficient to prevent or stop bleeding. Side effects included urticaria (one patient) and moderate anaphylactoid reaction (one patient). No evidence of plasma-born viral infections was observed up to 12 months after the treatment (95% confidence limits 0-22%). Calculated mean half-life of coagulation factors VII, X and XI was 4.36 h, 49.21 h and 44.5 h, respectively, similar to that observed with fresh-frozen plasma. Because of retained coagulation factor integrity and improved viral safety, S/D plasma could be considered a superior alternative to standard fresh-frozen plasma.