Case 8: Isolated prolongation of the activated partial thromboplastin time in a patient with a bleeding history – severe Factor XI deficiency

1999 ◽  
Vol 56 (9) ◽  
pp. 502-504 ◽  
Author(s):  
Redondo ◽  
Solenthaler ◽  
Zeerleder ◽  
Wuillemin
Keyword(s):  
Partial Thromboplastin Time ◽  
Activated Partial Thromboplastin Time ◽  
Factor Xi ◽  
Factor Xi Deficiency ◽  
Aktivierte Partielle Thromboplastinzeit ◽  
Bleeding History ◽  
Von Willebrand ◽  
Faktor Viii ◽  
Präoperative Abklärung

Ein 47jähriger Patient mit einer Anamnese von mehreren Episoden von revisionsbedürftigen postoperativen Nachblutungen nach Tonsillektomie, Sakraldermoidexzision und einem retroperitonealen Hämatom nach Operation einer Blasenhalsstenose, wurde wegen eines mechanischen Ileus auf die Abteilung für Viszeralchirurgie überwiesen, wo die Indikation für eine notfallmäßige Laparotomie gestellt wurde. Die präoperative Abklärung zeigte eine verlängerte aktivierte partielle Thromboplastinzeit (aPTT) von 93 Sekunden (Norm: 40–60 Sekunden), einen normalen Quickwert und eine normale Thrombinzeit. Im Mischversuch durch Zugabe von Normalplasma zum Patientenplasma normalisierte sich die aPTT, was mit einem Faktorenmangel vereinbar ist. Aufgrund der Anamnese und der verlängerten aPTT kommt differentialdiagnostisch ein Mangel an Faktor VIII, Faktor IX, Faktor XI oder ein von Willebrand Faktor-Mangel mit sekundär erniedrigtem Faktor VIII in Frage. Die Analyse der Gerinnungsfaktoren ergab einen schweren Faktor XI-Mangel von 4%. Unter Substitution mit frisch gefrorenem Plasma (FFP) konnte die Laparotomie ohne hämorrhagische Komplikationen durchgeführt werden.

Low- and Medium-molecular-weight Hydroxyethyl Starches

2000 ◽  
Vol 93 (5) ◽  
pp. 1231-1237 ◽  
Author(s):  
Marina Jamnicki ◽  
Thomas Bombeli ◽  
Burkhardt Seifert ◽  
Andreas Zollinger ◽  
Vladimir Camenzind ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Von Willebrand Factor ◽  
Partial Thromboplastin Time ◽  
Maximum Amplitude ◽  
Activated Partial Thromboplastin Time ◽  
Low Molecular Weight ◽  
Angle Alpha ◽  
Molar Substitution ◽  
Von Willebrand ◽  
Willebrand Factor

Background High-molecular-weight hydroxyethyl starch (HES) compromises blood coagulation more than medium-molecular-weight HES. The authors compared medium molecular weight HES (200 kd [HES200]) and low-molecular-weight HES (70 kd [HES70]). Methods In a prospective, double-blind, randomized-sequence crossover study, 22 male volunteers received 15 ml/kg HES200 and HES70. Blood samples were taken before and 5 min, 30 min, 1 h, 2 h, 4 h, 8 h, and 24 h after infusion. The following parameters were analyzed at all time points: prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII, antigenetic and functional von Willebrand factor, platelets, Thrombelastograph analysis parameters (reaction time, coagulation time, maximum amplitude, angle alpha, and clot lysis 30 and 60 min after maximum amplitude), ionized calcium, hematocrit, HES plasma concentration, molecular weight (weight average and number average), molar substitution, and polydispersity (weight average/number average). Repeated-measures analysis of variance (P < 0.05) was used to compare the response of the aforementioned parameters to the infusion of HES70 and HES200. Results Both HES solutions had a significant impact on all parameters. A slightly greater compromise with HES200 was found in activated partial thromboplastin time (P = 0.010), factor VIII (P = 0.009), antigenetic von Willebrand factor (P = 0.041), functional von Willebrand factor (P = 0.026), maximum amplitude (P = 0.008), and angle alpha (P = 0.003). No difference was established with the other parameters. HES concentration (P < 0.001), weight average (P < 0.001), number average (P < 0.001), and polydispersity (P < 0.001) were higher with HES200. There was no difference with molar substitution (P = 0.091). Conclusions Low-molecular-weight hydroxyethyl starch (70 kd) compromises blood coagulation slightly less than HES200, but it is unclear whether this is clinically relevant.

scholarly journals Pseudo-factor-XI deficiency: effect of an inhibitor of factor XI adsorption to surface

Blood ◽  
1981 ◽  
Vol 57 (3) ◽  
pp. 437-443
Author(s):  
S Schiffman ◽  
R Margalit ◽  
M Rosove ◽  
D Feinstein
Keyword(s):  
Partial Thromboplastin Time ◽  
Gel Filtration ◽  
Glass Tube ◽  
Factor Xii ◽  
Contact Activation ◽  
Factor Xi ◽  
Factor Xi Deficiency ◽  
Normal Plasma

Recently we have described a normal plasma activity that modulates contact activation by inhibiting adsorption of factor XI to activating surfaces. Here we report the first identified case in which a patient has abnormal clotting tests due to an excess of a similar activity. The patient's plasma had a prolonged partial thromboplastin time and low apparent factor XI assay. His plasma prolonged the partial thromboplastin time of normal plasma and partially neutralized normal factor XI activity in vivo and in vitro. Analysis in dilute plasma revealed normal amounts of factor XI activity and antigen. Factor XI adsorption from plasma to activating surfaces was tested by adding a small amount of 125I-labeled purified factor XI to plasma, exposing the mixture to a glass tube or kaolin, and determining the amount of factor XI adsorbed to the surface. Whereas normal plasma and plasmas deficient in factor XII, factor XI, or Fletcher factor yielded about 4% adsorption to glass, factor XI adsorption from patient's plasma was less than 1%, indicating the presence of an adsorption inhibitor. This inhibitor did not affect factor XI activation or the activity of preformed factor XIa. It was not adsorbed by AI(OH)3 and was present in serum and the macroglobulin peak on gel filtration of the plasma through Sephadex G-200. The patient's history does not allow a definitive conclusion as to whether this inhibitor was associated with abnormal bleeding.

Definition of the Bleeding Tendency in Factor XI-Deficient Kindreds–A Clinical and Laboratory Study

1995 ◽  
Vol 73 (02) ◽  
pp. 194-202 ◽  
Author(s):  
P H B Bolton-Maggs ◽  
D A Patterson ◽  
R T Wensley ◽  
E G D Tuddenham
Keyword(s):  
Convincing Evidence ◽  
Factor Vii ◽  
Bleeding Tendency ◽  
Factor Xi ◽  
Excessive Bleeding ◽  
North West ◽  
Factor Xi Deficiency ◽  
History Analysis ◽  
Definition Of ◽  
Von Willebrand

SummaryIndividuals with severe factor XI deficiency are prone to excessive bleeding after injury or surgery, but the existence of a haemorrhagic tendency in partial factor XI deficiency is controversial. In this study, 172 members of 30 kindreds (20 non-Jewish) transmitting factor XI deficiency in North West England were interviewed and a bleeding history questionnaire completed. Blood was taken for coagulation assays. The questionnaires were categorised independently by two assessors to determine presence or absence of a bleeding tendency, in the absence of information about the factor XI level or family history. Analysis shows that 48% of heterozygotes have a bleeding tendency. Eighteen (60%) families came to attention because of bleeding problems in heterozygotes. Comparison of histories between partially deficient and non-deficient individuals demonstrated a higher incidence of menstrual problems, an increase in significant bruising, and an increased likelihood of excessive bleeding after tonsillectomy and dental extractions.The incidence of von Willebrand’s disease was not increased, but individuals with heterozygous factor XI deficiency who were bleeders tended to have lower levels of factor VIIIc and von Willebrand factor, and were more commonly of blood group 0. These features may contribute to the bleeding tendency. There was no evidence of alteration in factor VII activity (as defined by the ratio of activity to antigen) between the bleeders and non-bleeders.This is convincing evidence for abnormal bleeding in factor XI deficiency which is not confined to severely deficient patients.

scholarly journals Identification of a defective factor XI cross-reacting material in a factor XI-deficient patient

Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 31-37 ◽  
Author(s):  
C Mannhalter ◽  
P Hellstern ◽  
E Deutsch
Keyword(s):  
Partial Thromboplastin Time ◽  
Complete Removal ◽  
Activated Partial Thromboplastin Time ◽  
The Other ◽  
Radial Immunodiffusion ◽  
Factor Xi ◽  
Normal Individuals ◽  
Coagulant Activity ◽  
Deficient Patient ◽  
Esterolytic Activity

Abstract A homozygous factor XI-deficient girl, who appeared to be positive for cross-reacting material (CRM+) was studied for clarification. Factor XI antigen (F XI:Ag) was measured by radial immunodiffusion using monospecific, heterologous anti-factor XI antibodies. Factor XI coagulant activity (F XI:C) was determined in a modified activated partial thromboplastin time (APTT) test. The ratio of F XI:C to F XI:Ag was 0.04 for the proposita, as compared with 0.7 to 0.74 in the other family members. In contrast, 12 normal individuals had ratios of F XI:C to F XI:Ag of 1.04 +/- 0.15. F XI esterolytic activity was clearly higher than F XI:C in the proband, but not in her relatives. Immunoblotting studies demonstrated F XI CRM in the patient's plasma. Chromatography on diethylaminoethanol (DEAE)-Sephadex at pH 8.4 led to an almost complete removal of F XI from the plasma. The defective F XI was not bound to a negatively charged kaolin surface due to an abnormal interaction with high-mol-wt kininogen (HMWK).

Von Willebrand Factor Antigen and Factor XI Activity Levels As Predictors of Bleeding Tendency in Israeli Patients with Von Willebrand's Disease

1995 ◽  
Vol 1 (4) ◽  
pp. 260-264 ◽  
Author(s):  
Benjamin Brenner ◽  
Tamar Stemberg ◽  
Arieh Laor ◽  
Shulamit Tavori ◽  
Ilana Tatarsky ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Von Willebrand Factor ◽  
Activity Levels ◽  
Factor Xi ◽  
Factor Xi Deficiency ◽  
Von Willebrand Factor Antigen ◽  
Von Willebrand ◽  
Induced Aggregation ◽  
Willebrand Factor ◽  
Factor Antigen

Previous preliminary data and case reports have suggested an association of von Willebrand's disease (vWD) with factor XI deficiency and platelet abnormalities. We have analyzed the prevalence of factor XI deficiency and thrombocytopathy in a cohort of Israeli patients with vWD. Decreased factor XI levels (<67 U/dl) were documented in 35 of 63 (36%) vWD subjects; factor XI levels were <30 U/dl in five of 60 (8%). A significant decline in ADP-induced platelet aggregation (<30% of control) was found in 48% of vWD patients. Likewise, epinephrine-induced aggregation was reduced in 41%, and collagen-induced aggregation was decreased in 7% of vWD patients. Logistic regression analysis showed that while Ivy bleeding time, ristocetin cofactor, and ristocetin-induced platelet aggregation did not predict bleeding, both von Willebrand factor antigen and factor XI activity levels predict bleeding in patients with vWD. These findings suggest that mild factor XI deficiency and thrombocytopathy are common in Israeli subjects with vWD and that associated factor XI deficiency can result in clinical bleeding in these patients. Key Words: Von Willebrand' s disease—Factor XI deficiency—Thrombocytopathy.

Coagulation Abnormalities in Patients with Noonan Syndrome - a Single Centre Case Series.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1035-1035
Author(s):  
Jayson M. Stoffman ◽  
Bernard N. Chodirker ◽  
Sara J. Israels
Keyword(s):  
Platelet Aggregation ◽  
Noonan Syndrome ◽  
Case Series ◽  
Protein S ◽  
Bleeding Tendency ◽  
Thrombin Time ◽  
Factor Xi ◽  
Factor Xi Deficiency ◽  
Coagulation Abnormalities ◽  
Von Willebrand

Abstract Noonan syndrome (NS) is an autosomal dominant disorder that includes short stature, characteristic facies, congenital heart defect, webbed neck, and developmental delay. A mutation in the PTPN11 gene can be identified in 50% of patients. A bleeding tendency is included in the phenotypic spectrum, with factor XI deficiency and platelet abnormalities described most frequently. At Winnipeg’s Health Sciences Centre, 24 patients with features typical of NS have been studied by the Special Haemostasis Laboratory. Four patients in whom the diagnosis was suspected but not considered definite are also included in this analysis. Clinical complaints included easy bruising (9), epistaxis (2), menorrhagia (1), and a family history of bleeding problems (3). Sixteen patients were referred for investigation following the diagnosis of NS. All 28 patients had coagulation screening tests: 16 patients had an abnormal PT and 12 had an abnormal aPTT. Thrombin time was slightly prolonged in 6 of 23 patients. Reptilase time was normal in 8 patients, and fibrinogen concentration was normal in 20 patients. Factor XI levels were measured in 14 patients, with a mean value of 62% (range 32–99%). Only 2 patients had levels below the normal range. One of 13 patients evaluated for FXII levels was deficient (FXII 25%), and 2 of 19 patients evaluated for FIX levels had mild FIX deficiency (FIX 40 and 49%) without symptomatic bleeding. No other factor deficiencies were identified. Twenty-four patients had determinations of von Willebrand Factor antigen and activity; 2 had results consistent with mild Type 1 von Willebrand Disease. Platelet aggregation studies were done in 22 patients. A variety of abnormalities were noted, with the most frequent being abnormal aggregation with epinephrine (7/22). Dense granule number was decreased in 2 of 7 samples studied by electron microscopy. Lupus anticoagulants were detected in 3 of 13 patients screened. Thrombophilia investigations in 4 patients detected decreased protein S in one patient who had been diagnosed previously with protein S deficiency. This unselected case series, the largest reported to date in the literature, illustrates the heterogeneity of coagulation abnormalities that may occur in NS. Symptoms, when present, were mild, and often did not correlate with laboratory abnormalities. Non-specific platelet aggregation defects were the most commonly identified abnormalities. In contrast to the literature, factor XI deficiency was not prevalent. A specific etiology for the variable bleeding tendency has not yet been identified in NS.

scholarly journals HAEMOPHILIA

2013 ◽  
Vol 4 (3) ◽  
Author(s):  
Diana S Purwanto
Keyword(s):  
Factor Viii ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Activated Partial Thromboplastin Time ◽  
Factor Ix ◽  
Haemophilia A ◽  
Clotting Time ◽  
Serial Test ◽  
Faktor Viii ◽  
Hemofilia A

Abstrak: Hemofilia adalah kelainan perdarahan kongenital yang disebabkan oleh kekurangan faktor VIII (faktor antihemofilik) yang terkait dengan Hemofilia A, atau faktor IX (faktor Christmas) yang terkait dengan Hemofilia B. Kedua hemophilia diturunkan secara X-linked resesif, dan umumnya ditemukan pada laki-laki. Kami melaporkan kasus seorang anak berusia 4 tahun dengan riwayat memar, pendarahan berlebihan, disertai pembengkakan sendi yang nyeri dan hematoma otot, yang dicurigai mengidap hemofilia. Serial tes koagulasi dilakukan dengan hasil: jumlah trombosit, waktu perdarahan, prothrombin time (PT), thrombin clotting time (TCT), dan fibrinogen normal, sedangkan activated partial thromboplastin time (APTT) memanjang. Mixing studies dikoreksi ketika plasma normal dan adsorbed plasma ditambahkan ke plasma pasien, yang menunjukkan defisiensi faktor VIII merupakan penyebab hemofilia ini. Aktivitas faktor VIII 8% menegaskan suatu hemofilia A derajat ringan. Kata kunci: hemofilia, PT, APTT, mixing studies, faktor VIII.   Abstract: Haemophilia is a congenital bleeding disorder caused by a deficiency of factor VIII (antihaemophilic factor), which is related to haemophilia A, or factor IX (Christmast factor), associated with haemophilia B. Both X-linked are recessive, and males are affected mostly. In this case, a four year old boy, who had a history of excessive bruising and bleeding, also suffered from painful swelling of joints and muscle hematoma. He was diagnosed of suspected  haemophilia. A serial test of coagulation studies was performed. The results of platelet count, skin bleeding time, prothrombin time, thrombin clotting time, and fibrinogen were normal; whereas, the activated partial thromboplastin time was prolonged. The mixing studies were corrected when normal plasma and adsorbed plasma were added to the patient plasma, suggesting that the factor VIII deficiency was the cause of this haemophilia. The factor VIII activity was 8% which confirmed the evidence of mild haemophilia A. Keywords: haemophilia, PT, APTT, mixing studies, factor VIII.

The Effect of Combined Factor XI Deficiency with von Willebrand Factor Abnormalities on Haemorrhagic Diathesis

1990 ◽  
Vol 63 (01) ◽  
pp. 036-038 ◽  
Author(s):  
Shulamith Tavori ◽  
Benjamin Brenner ◽  
llana Tatarsky
Keyword(s):  
Platelet Aggregation ◽  
Von Willebrand Factor ◽  
Bleeding Tendency ◽  
Factor Xi ◽  
Factor Xi Deficiency ◽  
Haemorrhagic Diathesis ◽  
Von Willebrand’S Factor ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor

SummaryTo account for the lack of correlation between the level of factor XI (FXI) in deficient patients and haemorrhagic manifestations, we correlated the prevalence of combined FXI and von Willebrand’s factor (vWF) deficiency in 212 FXI-deficient patients. Fifty-four patients had a combined FXI and vWF deficiency: 16 patients had severe and 38 patients had mild FXT deficiency. In a group of 28 patients with comparably mild FXI deficiency, 14 bleeders had significantly lower mean vWF, Ag, ristocetin cofactor and ristocetin induced platelet aggregation than 14 non-bleeders selected on the basis of comparable FXI levels. These findings suggest that the combination of FXI and vWF deficiency is common and may affect the bleeding tendency in mild FXI deficiency.

Pseudo-factor-XI deficiency: effect of an inhibitor of factor XI adsorption to surface

Blood ◽  
1981 ◽  
Vol 57 (3) ◽  
pp. 437-443 ◽  
Author(s):  
S Schiffman ◽  
R Margalit ◽  
M Rosove ◽  
D Feinstein
Keyword(s):  
Partial Thromboplastin Time ◽  
Gel Filtration ◽  
Glass Tube ◽  
Factor Xii ◽  
Contact Activation ◽  
Factor Xi ◽  
Factor Xi Deficiency ◽  
Normal Plasma

Abstract Recently we have described a normal plasma activity that modulates contact activation by inhibiting adsorption of factor XI to activating surfaces. Here we report the first identified case in which a patient has abnormal clotting tests due to an excess of a similar activity. The patient's plasma had a prolonged partial thromboplastin time and low apparent factor XI assay. His plasma prolonged the partial thromboplastin time of normal plasma and partially neutralized normal factor XI activity in vivo and in vitro. Analysis in dilute plasma revealed normal amounts of factor XI activity and antigen. Factor XI adsorption from plasma to activating surfaces was tested by adding a small amount of 125I-labeled purified factor XI to plasma, exposing the mixture to a glass tube or kaolin, and determining the amount of factor XI adsorbed to the surface. Whereas normal plasma and plasmas deficient in factor XII, factor XI, or Fletcher factor yielded about 4% adsorption to glass, factor XI adsorption from patient's plasma was less than 1%, indicating the presence of an adsorption inhibitor. This inhibitor did not affect factor XI activation or the activity of preformed factor XIa. It was not adsorbed by AI(OH)3 and was present in serum and the macroglobulin peak on gel filtration of the plasma through Sephadex G-200. The patient's history does not allow a definitive conclusion as to whether this inhibitor was associated with abnormal bleeding.

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