Hereditary Spherocytosis (HS) Associated with a Heterozygous MTHFR C677T Mutation and with Elevated Anticardiolipin Antibodies.

Abstract Abstract 5069 Background Hereditary spherocytosis (HS) is a spectrum of inherited erythrocyte membrane defects that result in hemolysis and varying degrees of anemia, usually not associated with increased thrombotic risk. However, there is some concern about post-splenectomy thrombocytosis, since both arterial and venous thromboembolic events have been reported in patients splenectomized for HS. A review of the medical literature revealed only a few cases of thrombosis associated with pregnancy and hereditary spherocytosis, and none of them had methyl tetrahydrofolate reductase (MTHFR) mutations or the presence of elevated anticardiolipin antibodies (both considered risk factors for thromboembolic disease). Methods Case report Results A 34-year-old Caucasian female with history of hereditary spherocytosis and splenectomy at age five, underwent evaluation for infertility. The patient was found to have a high titer of anticardiolipin antibodies and the presence of heterozygosity for the MTHFR C677T mutation. She denied any personal or family history of deep venous thrombosis. Subsequently the patient became pregnant. Because the combination of thrombophilic states appears to increase the risk of thromboembolic events, it was decided to start the patient prophyllactically with oral aspirin 81 mg daily, Foltx® (Folic acid 2.5 mg, cyanocobalamin 2000 mcg, and pyridoxine hydrochloride 25 mg), and heparin 5000 mg subcutaneously twice a day. On her most recent evaluation, at 26 weeks of pregnancy, no medical or obstetric problems have been observed. Conclusion Our case illustrates an unusual combination of thrombophilic states. Further studies are needed to evaluate the clinical significance of this association. Disclosures No relevant conflicts of interest to declare.

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Venous Thromboembolic Events in Women Using the NuvaRing®.

Blood ◽

10.1182/blood.v110.11.3994.3994 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3994-3994

Author(s):

Merrill K. Shum ◽

Kumar Rajagopalan ◽

Neil A. Lachant

Keyword(s):

Factor V Leiden ◽

Protein S ◽

Anticardiolipin Antibodies ◽

Factor V ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic ◽

Swedish Medical ◽

Life Threatening ◽

History Of ◽

Unknown Unknown

Venous thromboembolic events (VTEs) are serious adverse effects seen in some women using oral contraceptives. Although the novel vaginal ring, (NuvaRing®) has been reported to be effective and well tolerated, the risks of VTEs are unknown. We report 3 women who developed potentially life-threatening VTEs (2 with pulmonary emboli and 1 inferior vena cava thrombus) while on the NuvaRing®. VTEs occurred 22 days, 3 months and 3 months after NuvaRing® insertion. None had a personal or family history of VTEs. Extensive thrombophilia evaluation showed 1 with heterozygous factor V Leiden and 2 with a transient lupus anticoagulant. 2 had a personal history of multiple miscarriages and all 3 had an elevated body mass index > 26. Searching Pubmed, Ovid and Medline, there have been 10 other reported cases of VTEs, in women using the vaginal ring (see table below). Risk factors reported by other authors include anticardiolipin antibodies, protein S deficiency, heterozygous prothrombin 20210, heterozygous factor V Leiden and prolonged air travel. With limited follow up, the true incidence of VTEs in women using the NuvaRing® is difficult to determine. However, in 2005 the Swedish Medical Products Agency reported a relative incidence of 5.3 cases per 10,000 women years for VTE complications. In summary, we report 3 women who had life-threatening VTEs associated with the use of the NuvaRing®. Longer follow-up of safety studies and post-marketing adverse event reporting are needed to determine VTE risks and incidence while using the NuvaRing®. Studies reporting VTEs in women using the NuvaRing® Source Number of patients VTE risk factors Family history Site Bjarnadottir et al, 2002 1/121 Unknown Unknown LE DVT Tuppurainen el al, 2004 1/40 Unknown Unknown LE DVT Oddsson et al, 2005 1/512 Unknown Unknown LE DVT Miller et al, 2005 1/429 Anticardiolipin antibodies, protein S deficiency Grandmother with DVT LE DVT Ahrendt et al, 2006 1/499 Double heterozygous factor V Leiden/prothrombin 20210, prolonged air travel Unknown LE DVT Roumen et al, 2006 1/854 Unknown Unknown Cerebral sinus thrombosis Samuelsson et al, 2007 1 Heterozygous prothrombin 20210 None Axillary vein DVT Swedish Medical Products Agency, 2005 4/? Unknown Unknown DVTs Shum et al, 2007 3 Obesity (3), Personal history of miscarriages (2), heterozygous factor V Leiden (1) 1 sister with miscarriage Bilateral pulmonary emboli (2), Iliac vein-IVC thrombus (1)

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Management Of Pregnancy In Patients With Antithrombin Deficiency

Blood ◽

10.1182/blood.v122.21.216.216 ◽

2013 ◽

Vol 122 (21) ◽

pp. 216-216

Author(s):

Mario von Depka ◽

Stefanie Döpke ◽

Anja Henkel-Klene ◽

Cornelia Wermes ◽

Mahnaz Ekhlasi-Hundrieser ◽

...

Keyword(s):

High Risk ◽

Pregnancy Loss ◽

Conflicts Of Interest ◽

Fetal Loss ◽

Bleeding Complications ◽

Thromboembolic Events ◽

Increased Risk ◽

History Of ◽

At Deficiency ◽

The Mean

Abstract Introduction During pregnancy women have a four- to five-fold increased risk of thromboembolism (TE) compared to women who are not pregnant. Among the most important risk factors for TE in pregnancy is the presence of thrombophilia. Multiple reports have described an association between antithrombin (AT) deficiency and an increased rate of thromboembolic events especially during pregnancy. As the placental development depends on well-balanced pro- and anticoagulant mechanisms, thrombophilia, e.g. AT deficiency may be associated with poor pregnancy outcome. Despite anticoagulation with low molecular weight heparin (LMH) during pregnancy and the postpartum period alone, women with AT deficiency are still at a high risk to develop TE, especially perinatal and during puerperium because of withheld anticoagulation to prevent bleeding complications. Therefore, several guidelines recommend the administration of antithrombin concentrates during high risk situations as pregnancy. Here, we present the results of our study on the usage of AT concentrates in pregnant women with AT deficiency who either suffered from fetal loss or thromboembolism prior inclusion. Methods In total, 22 pregnancies in 19 patients (age: 31.9±4.7; 22-41) with AT deficiency were included in this open-label, single-center study. Ten patients (53%) had a history of fetal loss, 9/19 (47%) patients hat a history of thromboembolism. During all pregnancies AT concentrate (AT-C) was administered, in 18/22 (81.8%) pregnancies LMH was given in addition. Prior pregnancy losses (21/30, 70%) occurred in all trimester (t1: n=11, t2: n=5, and in t3: n=5). Historical live birth rate (LBR) was 30%. Blood samples were collected in all trimesters and postpartum to analyze AT activity and antigen, endogenous thrombin potential (ETP), thrombin-antithrombin-complex (TAT), Fragment 1+2 (F1+2) and c-reactive protein test (CRP). A total of 114 uneventful pregnancies of 113 healthy women served as controls. Furthermore, the mean doses of AT concentrates/kg BW and the mean total number of infusions were calculated. Results In total, 21 pregnancies (95.5%) were successful. Mean total requirement of AT concentrate per pregnancy was 79.454 IU (range: 3.000-272.000 IU) during 27.8 treatment days per pregnancy (range: 1-88). Our data show an increase of F1+2 in the course of pregnancy. Mean levels of F1+2 at t1, t2 and t3 (t1= 255.9 ± 107.6, t2= 360.9 ± 117.4, t3= 545.3 ± 220.3 pmol/L) were significantly higher than in controls (t1= 82.2 ± 43, t2= 140 ± 100.2, t3= 183.5 ± 103.1, p<.001). Mean level of TAT was higher (3.1 ± 1.4 ng/mL) than in controls (1.7 ± 1.6 ng/mL, p=.001) in t1, whereas mean TAT in t2 and t3 was lower than in controls (3.8 ± 1.3 vs. 4.8 ± 1.9, p=.03; 5.0 ± 1.4 vs. 6.1 ± 3.0 ng/mL, n.s., resp.). No thromboembolic events occurred. In patients receiving AT-C, LBR increased from 30% to 95.5% (p<0.001) with a relative risk of 49.0 to develop pregnancy loss without anticoagulant treatment (5.7 – 421.8; 95% CI). Conclusion In patients with AT deficiency receiving AT concentrate and LMH we could demonstrate a significant increase of LBR from 30% to 95.5%. Furthermore, no thromboembolic events occurred, though almost half of the patients had a history of thromboembolism. There was no clear evidence of increased hypercoagulability. We conclude that combined AT concentrate and LMH are safe and efficacious for mother and child in preventing thromboembolism and pregnancy loss. Further studies to evaluate the exact mode of anticoagulation and benefit of combining AT concentrate and LMH are warranted. Disclosures: No relevant conflicts of interest to declare.

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Lupus Anticoagulants/Antiphospholipid-Protein Antibodies: The Great Imposters

Lupus ◽

10.1177/096120339600500519 ◽

1996 ◽

Vol 5 (5) ◽

pp. 431-435 ◽

Cited By ~ 28

Author(s):

DA Triplett

Keyword(s):

Solid Phase ◽

Fetal Loss ◽

Annexin V ◽

Protein S ◽

Anticardiolipin Antibodies ◽

Thromboembolic Events ◽

Lupus Anticoagulants ◽

Recurrent Fetal Loss ◽

Clinical Complications ◽

Venous Thromboembolic Events

Antiphospholipid-protein antibodies (APA) represent a family of immunoglobulins which recognize protein-phospholipid complexes. A variety of proteins have been implicated including: prothrombin, annexin V, β2-Glycoprotein I, and protein S. APA are detected utilizing either coagulation-based tests to identify lupus anticoagulants (LA) or solid phase ELISA assays to identify anticardiolipin antibodies (ACA). APA may be seen in a variety of different clinical settings including convalescence from infections, resulting from exposure to certain drugs, or in association with autoimmune diseases. Autoimmune APA have been linked to a variety of thromboembolic complications involving both arterial and venous sites. In addition, recurrent fetal loss has been linked to a APA. The underlying pathophysiology of the thromboembolic events remains controversial. Given the diversity of anatomic sites, more than one thromboembolic mechanism(s) is likely. Abnormalities of the protein C system most likely account for the venous thromboembolic events. Because of the spectrum of clinical complications, virtually any clinician may encounter patients with the APA syndrome (thrombosis, thrombocytopenia, recurrent fetal loss coupled with positive LA or ACA testing).

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Thromboembolic Outcomes of Hospitalized COVID-19 Patients in the 90-Day Post-Discharge Period: Early Data from the Northwell CORE-19 Registry

Blood ◽

10.1182/blood-2020-141901 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 33-34

Author(s):

Dimitrios Giannis ◽

Steven L. Allen ◽

Anne Davidson ◽

Galina S. Marder ◽

Sarah Flint ◽

...

Keyword(s):

Major Bleeding ◽

Small Sample ◽

Hospitalized Patients ◽

Hospital Treatment ◽

Common Data Model ◽

Thromboembolic Events ◽

Post Discharge ◽

Thrombotic Risk ◽

Venous Thromboembolic Events ◽

All Cause Mortality

Introduction Thromboembolic outcomes have emerged as an important issue in sick hospitalized patients with COVID-19. Multiple pathogenetic mechanisms for thrombosis have been implicated, including endothelial dysfunction, increased von Willebrand factor (vWF), interleukin-6 release, and activation of/interaction between macrophages, monocytes, endothelial cells, platelets and lymphocytes. The actual rate of arterial and venous thromboembolic events (ATE and VTE) in hospitalized patients with COVID-19, especially in the immediate post-hospital discharge period, has not been fully elucidated, with most of the data derived from retrospective studies with small sample sizes. Methods Against this background, we have designed and implemented an ongoing prospective registry (CORE-19) consisting of 11,249 consecutive hospitalized patients with COVID-19 from March 1st 2020 through May 31st 2020 using data derived from the Northwell Health System and the COVID-19 Research Consortium to study through 90-days post-discharge the rate of VTE and ATE, major bleeding, all-cause mortality, and other complications. We are capturing data of interest including demographic characteristics, co-morbidities, relevant medications, hospital setting, in-hospital treatment, thromboprophylaxis usage, key laboratory parameters, and 90-day thromboembolic and other key outcomes. A unified data repository (datamart) of hospitalized COVID-19 patients across multiple datasets from electronic health records, health informatics exchange, a dedicated radiology database, and a standardized data collection tool in REDCap, that includes telephonic calls up to 90 days post-discharge, is being implemented. A common data model (CDM) is utilized to ensure semantic interoperability between data originating from disparate sources. Northwell Health protocols stipulate the use of post-discharge low-molecular weight heparin, direct oral anticoagulants, or baby aspirin in hospitalized COVID-19 patients with high thrombotic risk features. Results Our cohort as of August 7, 2020 consists of complete follow up in 4,100 patients with a mean age of 61.0 years (SD: 17.0) with 54.7% males (Table 1). Preliminary data show an all-cause mortality rate of 4.29%, an overall thromboembolic rate of 3.51% (2.41% VTE and 1.10% ATE), a major bleeding rate of 1.61%, and a rehospitalization rate of 12.85%. Of patients with either DVT or PE post-discharge, 13.43% (9/67) died. The full dataset, including risk factors, comorbidities, key in-hospital and post-discharge medications including anticoagulant and antiplatelet agents, will be available at the time of presentation to the ASH congress. Conclusion Our ongoing registry is a large prospective study evaluating the rate of overall thromboembolic complications and all-cause mortality in hospitalized COVID-19 patients through 90 days post discharge. Current rates of thromboembolic events signify the importance of post-discharge surveillance and, potentially, post-discharge extended thromboprophylaxis, in this acutely ill medical population. Disclosures Allen: Bristol Myers Squibb: Current equity holder in publicly-traded company. Spyropoulos:Janssen, Boehringer Ingelheim, Bayer, BMS, Portola, ATLAS Group: Consultancy; Janssen, Boehringer Ingelheim: Research Funding.

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F5 Sequence Variant Identified in 7 Patients Evaluated for Hypercoagulable State with a Factor V (FV) HR2 Assay

Blood ◽

10.1182/blood-2018-99-114203 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5053-5053

Author(s):

Margaret M. Leech ◽

Daniel B. Bellissimo ◽

John A. Uhrmacher ◽

Sriya W. Gunawardena ◽

Michael J. Meyer ◽

...

Keyword(s):

Sanger Sequencing ◽

Conflicts Of Interest ◽

Restriction Pattern ◽

Sequence Variant ◽

Factor V ◽

The Novel ◽

Thrombotic Risk ◽

Pcr Product ◽

Clinical Consequences ◽

History Of

Abstract A 15-year-old African-American male with a history of thrombosis was examined for the Factor V HR2 sequence variation (c.3980A>G, p.H1327R) using PCR followed by RsaI digestion. An anomalous restriction pattern was observed: one strand was uncut (wild type) and the other was cleaved once. However, the fragment sizes were 516bp and 312bp instead of the 447bp and 381bp expected from HR2. Sanger sequencing of the PCR product detected a sequence variant (c.3845A>G) in this patient that creates a RsaI site explaining the novel band pattern. The c.3845A>G variant is found within one of four 27bp repeats found in exon 13 of the F5 gene. The HR2 variant is also present in one of the repeats. In this patient's case, the cleavage occurred in an abnormal location (c.3845A>G instead of c.3980A>G), creating the novel banding pattern observed. Six additional patients being tested for hypercoagulable states were evaluated with the FV HR2 assay and were found to have the same abnormal restriction pattern. The ethnicity of these other patients was not available to our laboratory. Sanger sequencing confirmed the presence of c.3845A>G sequence variant in each of these patients. Unlike the HR2 and FV Leiden variants, the c.3845A>G, p.H1282R variant (rs143333036) is most common in African populations (Minor Allele Frequency 0.012) but the clinical consequences of this variant are unclear. The variant lies within a 27bp repeat similar to the HR2 site and might cause it to be associated with a thrombotic risk similar to the HR2 variant. Further investigation will be required to determine whether the c.3845A>G variant is a population variant with no clinical consequences or whether it represents a genetic prothrombotic risk factor in certain patient populations. Nevertheless, in the laboratory the c.3845A>G, p.H1282R sequence variant may confound results when testing patients for the HR2 (rs1800595) variation. Disclosures No relevant conflicts of interest to declare.

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Antiphospholipid syndrome and pregnancy

Orvosi Hetilap ◽

10.1556/oh.2012.29425 ◽

2012 ◽

Vol 153 (31) ◽

pp. 1207-1218

Author(s):

Klára Gadó ◽

Gyula Domján

Keyword(s):

Antiphospholipid Syndrome ◽

Intrauterine Growth Restriction ◽

Recurrent Miscarriage ◽

Fetal Distress ◽

Normal Pregnancy ◽

Healthy Children ◽

Thromboembolic Events ◽

Thrombotic Risk ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic

Antiphospholipid syndrome is characterized by arterial and venous thromboembolic events and persistent laboratory evidence of antiphospholipid antibodies. Obstetric complications such as recurrent miscarriage, early delivery, oligohydramnios, prematurity, intrauterine growth restriction, fetal distress, fetal or neonatal thrombosis, pre-eclampsia/eclampsia, and HELLP syndrome are also hallmarks of antiphospholipid syndrome. This syndrome is one of the diseases associated with the most severe thrombotic risk. Changes in the hemostatic system during normal pregnancy also result in a hypercoagulable state resulting in elevated thrombotic risk. Thromboembolic events are responsible of the vast majority of maternal and fetal deaths. Administration of appropriate thromboprophylaxis helps prevent thromboembolic complications during pregnancy in women with antiphospholipid syndrome and also give birth to healthy children. It is important to centralize the medication and management of these patients. It helps in the thoughtful care of these pregnant women encountering serious problems. Orv. Hetil., 2012, 153, 1207–1218.

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Prevalence of the MTHFR C677T Mutation in Fertile and Infertile Women

Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics ◽

10.1055/s-0037-1606289 ◽

2017 ◽

Vol 39 (12) ◽

pp. 659-662 ◽

Cited By ~ 3

Author(s):

Adriana Soligo ◽

Ricardo Barini ◽

Joyce Annichino-Bizzacchi

Keyword(s):

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Mthfr Gene ◽

Control Group ◽

Case Group ◽

Infertile Women ◽

Chi Squared ◽

History Of ◽

C677t Mutation ◽

Fertile Women

Introduction The importance of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in infertile women remains controversial. Objective To evaluate if the MTHFR C677T mutations are more frequent in infertile women, and if they can be associated with the occurrence of infertility in the Brazilian population. Methods This case-control study included 130 infertile women consulting at a private clinic between March 2003 and March 2005 (data previously published), and 260 fertile women attending the family planning outpatient clinic of our institution between April 2012 and March 2013. Data analysis The Chi-squared and Fisher Exact tests were used to evaluate the association between the presence of the MTHFR C677T mutation and a history of infertility. Results The frequency of the mutation was of 58.5% for the case group (n = 76) and of 49.2% for the fertile controls (n = 128). The mutation was homozygous in 13 women in the case group (10%) and in 23 of the fertile women in the control group (8.8%). These differences were not statistically significant. Conclusions These results suggest that the presence of the MTHFR C677T mutation does not constitute a risk factor for infertility, even when the mutation is homozygous. Further studies are needed to confirm whether research on this mutation should be considered unnecessary in women with infertility.

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Factor V Leiden, Prothrombin 20210 G → A and the MTHFR C677T Mutations in Childhood Stroke

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614555 ◽

1999 ◽

Vol 81 (05) ◽

pp. 690-694 ◽

Cited By ~ 73

Author(s):

E. A. Chalmers ◽

A. Thomas ◽

A. Sproul ◽

C. Healey ◽

I. Rafferty ◽

...

Keyword(s):

Factor V Leiden ◽

Protein S ◽

Mthfr C677t ◽

Anticardiolipin Antibodies ◽

Mthfr Gene ◽

Factor V ◽

Large Prospective Study ◽

C677t Mutation ◽

Haematological Analysis

SummaryIschaemic 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.

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Characteristics of Rare Coagulation Factors Deficiency in Adults, an Experience from Qatar

Blood ◽

10.1182/blood-2020-137408 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 31-32

Author(s):

Shehab Fareed Mohamed ◽

Ahmed Abdalhadi ◽

Khalid Elhag ◽

Amna Gamil ◽

Abdulqadir Jeprel Nashwan ◽

...

Keyword(s):

Surgical Procedures ◽

Autosomal Recessive ◽

Conflicts Of Interest ◽

Adult Life ◽

Coagulation Factors ◽

Von Willebrand Disease ◽

Coagulation Cascade ◽

Coagulation Disorder ◽

Thrombotic Risk ◽

History Of

Background Rare factors (F) deficiencies are defined as deficiencies of factors other than F VIII or IX. They are inherited as autosomal recessive with a prevalence that varies between 1:500,000 to 1:2000,000.FI deficiency includes Afibrinogenemia, Hypofibrinogenemia and Dysfibrinogenemia. While most patients with dysfibrinogenemia don't bleed patients with afibrinogenemia can present with life threatening bleeding. FII deficiency can be acquired or inherited. the most frequent severe symptoms are muscle hematomas and hemarthrosis. With FV deficiency some patients may be asymptomatic while children with severe deficiency can present with CNS bleeding. Patients with low FV should also get their FVIII checked to rule out combined (F5F8) deficiency which is a separate rare coagulation disorder that results from a mutation in a protein that transfers both factors from the cell to the blood stream. Symptoms are generally mild and it rarely causes hematomas or hemarthrosis. FVII deficiency is the most common autosomal recessive coagulation disorder (1:500,000). The severity of symptoms is reported to be poorly correlated with the plasma levels. FX deficiency can present with serious bleeding manifestations. Options for treatment include fresh frozen plasma (FFP) or prothrombin concentrate. FXI deficiency (Hemophilia C) unlike F8 and F9 doesn't cause joint or muscle bleeding. Hemophilia C is the second most common bleeding disorder affecting women following Von Willebrand disease. The most common presentation of FXII deficiency is asymptomatic prolongation of aPTT. Deficiency of this factor carries a more thrombotic risk rather than bleeding because it plays a bigger role in initiation of fibrinolysis compare to its contribution to the coagulation cascade. Most patients with FXIII deficiency experience symptoms from birth often bleeding from the umbilical cord stump and bleeding symptoms tend to continue throughout life. Methodology Data was collected from hematology outpatients' clinics from January 2018 to June 2020. Patients above 18 years with rare factor deficiencies.were included in the study,We excluded FVIII and IX as it is less rare and there are specific guidelines for these patients.Data included were demographics, the factor deficient, level, surgical history and others. Results The total number is 29 patients. The mean age is 34 years (18-77). There is female predominance with 69 %. 65 % of the patients were Qataris and 36% from other nationalities. The most deficient factor is FI 41%, followed by FVII 20 %, then FXII and XIII. Interestingly we found one rare case of combined F5F8 deficiency in a Lebanese lady. Family history was positive in 41 % of cases, almost in all the cases of Fibrinogen deficiency. All the cases of Hypofibrinogenemia came from one qatari Tribe. 38 % of the patients had history of bleeding, while 80 % had surgical procedures. 55% received replacement therapy for bleeding or before procedures. Due to the history of transfusions we checked for HIV, HBV and HCV status and we found only one case with HCV. Conclusion Some factor deficiencies pose a challenge in hematology clinics due its rarity and lack of guidelines. Mild deficiency can be discovered for the first time in adult life, during surgery, pregnancy or gynecological procedures. Therefore, females are more likely to be discovered than males. Abnormalities in coagulation should be considered before surgical procedures, which might require hematologist consultation. Educating patients and physicians will help in preparing these patients and initiation of protocols if needed. Figure Disclosures No relevant conflicts of interest to declare.

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Clinical Outcomes and Factors Predicting Development of Venous Thromboembolic Complications in Patients with Advanced Refractory Cancer in a Phase I Clinic: The M. D. Anderson Cancer Center Experience

Blood ◽

10.1182/blood.v112.11.3828.3828 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3828-3828

Author(s):

Apostolia-Maria Tsimberidou ◽

Sushma Vemulapalli ◽

Lakshmi Chintala ◽

Navjot Dhillon ◽

Xiudong Lei ◽

...

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Phase I ◽

Hazard Ratio ◽

Cancer Center ◽

Thromboembolic Events ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic ◽

History Of ◽

Weighted Number

Abstract Venous thromboembolism (VTE) is common in patients with advanced cancer and may influence patient eligibility for clinical studies, quality of life, and survival. We reviewed the records of 220 consecutive patients seen in the Phase I Program at M. D. Anderson Cancer Center to determine the frequency of VTE, associated characteristics and clinical outcomes. Of 220 patients, 23 (10.5%) presented to the Phase I clinic with a history of VTE. Twenty-six patients (11.8%) subsequently developed a venous thromboembolic event, with a median follow-up of 8.4 months. These included 9 of 23 patients (39%) with and 17 of 197 (8.6%) without a history of VTE (p < 0.0001). The median time from the first visit to the Phase I clinic to a new thromboembolic episode in the 26 patients was 5.1 months (range, 0 to 27 months). The respective times to development of new thromboembolic events for patients with and without a history of thromboembolism were 3.1 months (n = 9) and 5.3 months (n = 17). Four (15%) of the 26 patients developed venous thromboembolism within one month after their first visit to the Phase I clinic. Among the remaining 22 patients, 18 (69%) developed venous thromboembolism within the first year following their initial visit to the Phase I clinic, and 4 patients developed it after 2.5 years. Fifteen patients developed DVT, seven pulmonary embolism (PE), and one patient each developed one of the following thromboembolic episodes: concurrent DVT and PE; right atrial thrombus; thrombus in the abdominal aorta and DVT; and isolated thrombus in an abdominal aortic aneurysm. The median survival in patients with and without a history of VTE were 4.7 and 10.9 months, respectively (p = 0.0002). Multivariate analysis demonstrated that a history of VTE (hazard ratio 6.2; 95% C.I. 2.6–14.7; p < 0.0001), diagnosis of pancreatic cancer (hazard ratio 4.0; 95% C.I. 1.5–11.2; p=0.007) and platelet count >440 × 109/L (hazard ratio 3.1; 95% C.I. 1.1–8.2; p = 0.026) predicted the development of new venous thromboembolic episodes. These three parameters were used to design a predictive model. Based on the relative risks of the independent covariates, the relative risk of a new thromboembolic episode could be characterized by summing the weighted number of risk factors present at first visit to the Phase I clinic. History of venous thromboembolism was given a score of 2 because the hazard ratio was 6.3, whereas the diagnosis of pancreatic cancer and elevated platelet counts had hazard ratios of 4.7 and 3.0, respectively, and were each given a score of 1. Therefore, patients could have a score ranging from 0 to 4 (no patients had a score of 4). Patients were assigned to one of three risk groups on the basis of their weighted number of presenting risk factors: 0, low risk; 1, medium risk; 2–3, high risk. At 6 months, the rates of a new thromboembolic episode were 3.5%, 12.5%, and 28% for patients with scores 0, 1, or 2–3, respectively (p<0.0001). The median time to a new thromboembolic episode was not reached for patients with a score 0 or 1, and it was 9.1 months for patients with a score of 2–3. In conclusion, a history of VTE or new development of VTE was noted in 40 (18%) of 220 patients seen in our Phase 1 clinic. Our study suggests the need to closely monitor individuals with advanced cancer for the development of venous thromboembolic events. The high risk of recurrent venous thromboembolism in patients with a prior history of venous thromboembolism, whose anticoagulation therapy was discontinued before clinic referral, supports long-term continued prophylaxis in these patients. A prognostic score to predict for time to and frequency of venous thromboembolic events is thereby proposed.

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