Quantification of the contribution of individual coagulation factors to haemostasis using a microchip flow chamber system and reconstituted blood from deficient plasma.

BACKGROUND AND OBJECTIVES: Quantifying the contribution of individual coagulation factors to haemostasis may aid our understanding of the haemostatic function in patients with rare coagulation deficiencies (RCDs) and the exploration of suitable treatments. MATERIALS AND METHODS: Reconstituted blood prepared from specific coagulation factor-deficient plasma (factor [F]II; prothrombin, FV, FVII, FVIII, FIX, FX, FXI or FXII) and red blood cell/platelet products were used to simulate the whole blood of patients with RCD. We prepared in vitro treatment models for patients with prothrombin deficiency using coagulation factor agents and fresh frozen plasma. Haemostatic function was measured using a microchip flow chamber system at 600 s-1. RESULTS: The haemostatic function was low, especially in blood samples reconstituted with prothrombin- and FX-deficient plasma. In a plasma transfusion model of prothrombin deficiency, haemostatic function recovered after 10% replacement with normal plasma and reached a plateau at ≧60% replacement. A treatment model of prothrombin deficiency with prothrombin complex concentrates revealed dose-dependent therapeutic effects in the range of 0-50 IU/kg. CONCLUSION: Microchip flow chamber system-based quantification of haemostatic function using reconstituted blood could predict haemostasis and therapeutic effects of treatments in patients with prothrombin deficiency.

APTT critical value establishment in four different reagent/instrument systems based on single factor deficiencies.

INTRODUCTION: There are significant differences in the activated partial thromboplastin time (APTT) critical values reported in different studies, most of which does not make recommendations for any specific clear detection systems. The International Council for Standardization in Hematology (ICSH) recommends that APTT critical values be established based on the reagent type, coagulation factor sensitivity and heparin response. The objective of this study was to establish APTT critical values by using different reagents and based on single coagulation factor deficiencies. METHODS: The APTT values were determined in commercial endogenous coagulation factor-deficient plasma at concentrations of 1 IU/dL, 2 IU/dL, 5 IU/dL, 10 IU/dL, 20 IU/dL, and 30 IU/dL by using four assay systems. The retrospective collection of data from patients who lacked factor VIII (FVIII), FIX, or FXI alone was performed. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic accuracy of APTT for identifying patients with an endogenous coagulation factor activity < 5 IU/dL. RESULTS: The APTT values in the plasma samples with the same concentrations of endogenous coagulation factors were significantly different among the four assay systems (P < 0.001). The suggested critical values of APTT were 40.0 s for Sysmex CS5100 (Actin FSL), 58.0 s for Sysmex CS5100 (Actin), 51.8 s for STA-R Evolution (STA-PTTA), and 64.8 s for ACL TOP 700 (HemosIL SynthasIL). On the basis of the ROC curve, the optimal threshold values for APTT (STA-PTTA) were 55.8 s in patients with a simple deficiency of FVIII (sensitivity = 100%, specificity = 85.7%, area under the ROC curve (AUC) = 0.982), 54.3 s in patients with a simple deficiency of FIX (sensitivity = 100%, specificity = 92.9%, AUC = 0.986), and 71.7 s in patients with a simple deficiency of FXI (sensitivity = 100%, specificity = 94.1%, AUC = 0.992), which were closer (difference of 0.6-2.5 s) to the cutoff points for commercial plasma at equal factor levels. CONCLUSIONS: APTT critical values need to be established for different reagents based on the presence of a single coagulation factor deficiency.

Comparative analysis of thrombin generation platforms for patients with coagulation factor deficiencies: A comprehensive assessment.

INTRODUCTION: Thrombin generation assays (TGAs) assess the overall functionality of the hemostatic system and thereby provide a reflection of the hemostatic capacity of patients with disorders in this system. Currently, four (semi-)automated TGA platforms are available: the Calibrated Automated Thrombogram, Nijmegen Hemostasis Assay, ST Genesia and Ceveron s100. In this study, we compared their performance for detecting patients with congenital single coagulation factor deficiencies. MATERIALS AND METHODS: Pooled patient samples, healthy control samples and normal pooled plasma were tested on all four platforms, using the available reagents that vary in tissue factor and phospholipid concentrations. The TGA parameters selected for analysis were peak height and thrombin potential. Results were normalized by using the calculated mean of healthy controls and a correction for between-run variation. Outcomes were presented as relative values, with the mean of healthy controls standardized to 100 %. RESULTS: Across all platforms and reagents used, thrombin potentials and peak heights of samples with coagulation factor deficiencies were lower than those of healthy controls. Reagents designed for bleeding tendencies yielded the lowest values on all platforms (relative median peak height 19-32 %, relative median thrombin potential 19-45 %). Samples representing more severe coagulation factor deficiencies generally exhibited lower relative peak heights and thrombin potentials. CONCLUSIONS: Thrombin generation assays prove effective in differentiating single coagulation factor deficient samples from healthy controls, with modest discrepancies observed between the platforms. Reagents designed for assessing bleeding tendencies, featuring the lowest tissue factor and phospholipid concentrations, emerged as the most suitable option for detecting coagulation factor deficiencies.

[Colonic pseudotumoral involvement as an expression of severe plasminogen deficiency]. / Compromiso pseudotumoral colónico como expresión de déficit grave de plasminogéno.

Plasminogen deficiency is a very rare multisystem entity that affects different tissues of the economy through the deposition of fibrin-rich pseudomembrane and determines a heterogeneous and diverse clinical presentation. It is transmitted in an autosomal recessive manner by mutations of the PLG gene on chromosome 6 and can be divided into hypoplasminogenemia or type I and dysplasminogenemia or type II, the latter not related to clinical pathology. Severe plasminogen deficiency has a prevalence of 1.6 individuals per million inhabitants and although it can be diagnosed in adulthood, the most severe symptoms are observed in infants and children. The most common form of onset is the so-called woody conjunctivitis, characterized by fibrin membranes that are deposited on the eyelids since childhood, causing exophytic lesions that affect vision. It can also affect other mucous membranes such as the gingival, respiratory, oropharyngeal, digestive and genital mucosa, among others. We present a rare case of severe plasminogen deficiency with conjunctivitis and woody cervicitis who was admitted with clinical acute abdominal symptoms, associated with a tumor mass due to pseudomembranous deposition in the ascending colon that simulated inflammatory bowel disease and resolved spontaneously.

La deficiencia de plasminógeno es una entidad multisistémica, muy infrecuente, que afecta diferentes tejidos de la economía mediante el depósito de pseudo membranas ricas en fibrina y que determina una presentación clínica heterogénea y diversa. Se transmite en forma autosómica recesiva por mutaciones del gen PLG del cromosoma 6 y se puede dividir en hipoplasminogenemia o tipo I y displasminogenemia o tipo II, esta última no relacionada con patología clínica. El déficit grave de plasminógeno tiene una prevalencia de 1.6 individuos por millón de habitantes y si bien puede diagnosticarse en edad adulta, los síntomas más graves se observan en lactantes y niños. La forma de inicio más común es la denominada conjuntivitis leñosa, caracterizada por membranas de fibrina que se depositan en los parpados desde la infancia, provocando lesiones exofíticas que afectan la visión. También puede afectar otras mucosas como la gingival, respiratoria, orofaríngea, digestiva y genital entre otros. Presentamos un raro caso de deficiencia grave de plasminógeno con conjuntivitis y cervicitis leñosa que ingresó con un cuadro de abdomen agudo clínico, asociado a una masa tumoral por depósito de pseudomembranas en el colon ascendente que simuló una enfermedad inflamatoria intestinal y que se resolvió espontáneamente.

A Successful Treatment Approach in 2 Patients With Type 1 Plasminogen Deficiency: Intratracheal Application of Fresh Frozen Plasma and Tissue Plasminogen Activator.

BACKGROUND: Respiratory system involvement is common in congenital plasminogen deficiency. Although many treatment approaches have been tried, there is still no definitive treatment for respiratory system involvement. OBSERVATIONS: We report 2 congenital plasminogen deficiency cases, who presented with severe respiratory symptoms, for whom a novel treatment modality was tried. After intravenous administration of FFP (fresh frozen plasma), tissue plasminogen activator and FFP were administered intratracheally, and respiratory system findings improved. CONCLUSIONS: Intratracheal administration of tissue plasminogen activator and FFP is an available treatment modality for patients with lung involvement. Fibrin plaques should be carefully removed and new lesion formation should be prevented.

Molecular basis of rare congenital bleeding disorders.

Rare bleeding disorders (RBDs), including factor (F) I, FII, FV, FVII, combined FV and FVIII (CF5F8), FXI, FXIII and vitamin-K dependent coagulation factors (VKCF) deficiencies, are a heterogeneous group of hemorrhagic disorder with a variable bleeding tendency. RBDs are due to mutation in underlying coagulation factors genes, except for CF5F8 and VKCF deficiencies. FVII deficiency is the most common RBD with >330 variants in the F7 gene, while only 63 variants have been identified in the F2 gene. Most detected variants in the affected genes are missense (>50% of all RBDs), while large deletions are the rarest, having been reported in FVII, FX, FXI and FXIII deficiencies. Most were located in the catalytic and activated domains of FXI, FX, FXIII and prothrombin deficiencies. Understanding the proper molecular basis of RBDs not only can help achieve a timely and cost-effective diagnosis, but also can help to phenotype properties of the disorders.

The first Moroccan case of severe type II congenital plasminogen deficiency with ligneous conjunctivitis.

Ligneous conjunctivitis (LC) is a rare form of pseudomembranous chronic conjunctivitis caused by a deficiency in plasminogen activity. Due to its rarity, little is known about this disorder. We hereby report a case of ligneous conjunctivitis, describing the clinical findings, the biological diagnosis and the treatment of this rare disease.

Ligneous conjunctivitis associated with type I plasminogen deficiency: A rare case.

Ligneous conjunctivitis is a rare form of chronic, recurrent conjunctivitis characterized by wood-like, fibrinous pseudomembranes, which may be associated with systemic disease manifestations. It has been associated with congenital plasminogen (PLG) deficiency that is inherited with an autosomal recessive pattern due to mutations in the PLG gene and a variety of other genes, leading to disturbed wound healing. In this case report, we present the clinical, laboratory, and histopathological findings of a 36-year-old female patient who presented at the ophthalmology department with complaints of redness, irritation for the previous few weeks, and appearance of membranous lesions mainly on the tarsal conjunctivae. During biomicroscopic examination we found thick, yellowish-white pseudomembranes, and conjunctival proliferation with ligneous induration on the conjunctiva, located on the upper eyelids. Histopathological evaluations showed up ligneous conjunctivitis and laboratory evaluation confirmed a severe plasminogen deficiency (PLG < 2%). The patient was treated with topical fresh frozen plasma (FFP), topical steroids, heparin eye drops, and artificial tear drops daily, without systemic therapy.

Investigating the Multifaceted Nature of Radiation-Induced Coagulopathies in a Göttingen Minipig Model of Hematopoietic Acute Radiation Syndrome.

Coagulopathies are well documented after acute radiation exposure at hematopoietic doses, and radiation-induced bleeding is notably one of the two main causes of mortality in the hematopoietic acute radiation syndrome. Despite this, understanding of the mechanisms by which radiation alters hemostasis and induces bleeding is still lacking. Here, male Göttingen minipigs received hematopoietic doses of 60Co gamma irradiation (total body) and coagulopathies were characterized by assessing bleeding, blood cytopenia, fibrin deposition, changes in hemostatic properties, coagulant/anticoagulant enzyme levels, and markers of inflammation, endothelial dysfunction, and barrier integrity to understand if a relationship exists between bleeding, hemostatic defects, bone marrow aplasia, inflammation, endothelial dysfunction and loss of barrier integrity. Acute radiation exposure induced coagulopathies in the Göttingen minipig model of hematopoietic acute radiation syndrome; instances of bleeding were not dependent upon thrombocytopenia. Neutropenia, alterations in hemostatic parameters and damage to the glycocalyx occurred in all animals irrespective of occurrence of bleeding. Radiation-induced bleeding was concurrent with simultaneous thrombocytopenia, anemia, neutropenia, inflammation, increased heart rate, decreased nitric oxide bioavailability and endothelial dysfunction; bleeding was not observed with the sole occurrence of a single aforementioned parameter in the absence of the others. Alteration of barrier function or clotting proteins was not observed in all cases of bleeding. Additionally, fibrin deposition was observed in the heart and lungs of decedent animals but no evidence of DIC was noted, suggesting a unique pathophysiology of radiation-induced coagulopathies. These findings suggest radiation-induced coagulopathies are the result of simultaneous damage to several key organs and biological functions, including the immune system, the inflammatory response, the bone marrow and the cardiovasculature.

A Clot Twist: Extreme Variation in Coagulotoxicity Mechanisms in Mexican Neotropical Rattlesnake Venoms.

Rattlesnakes are a diverse clade of pit vipers (snake family Viperidae, subfamily Crotalinae) that consists of numerous medically significant species. We used validated in vitro assays measuring venom-induced clotting time and strength of any clots formed in human plasma and fibrinogen to assess the coagulotoxic activity of the four medically relevant Mexican rattlesnake species Crotalus culminatus, C. mictlantecuhtli, C. molossus, and C. tzabcan. We report the first evidence of true procoagulant activity by Neotropical rattlesnake venom in Crotalus culminatus. This species presented a strong ontogenetic coagulotoxicity dichotomy: neonates were strongly procoagulant via Factor X activation, whereas adults were pseudo-procoagulant in that they converted fibrinogen into weak, unstable fibrin clots that rapidly broke down, thereby likely contributing to net anticoagulation through fibrinogen depletion. The other species did not activate clotting factors or display an ontogenetic dichotomy, but depleted fibrinogen levels by cleaving fibrinogen either in a destructive (non-clotting) manner or via a pseudo-procoagulant mechanism. We also assessed the neutralization of these venoms by available antivenom and enzyme-inhibitors to provide knowledge for the design of evidence-based treatment strategies for envenomated patients. One of the most frequently used Mexican antivenoms (Bioclon Antivipmyn®) failed to neutralize the potent procoagulant toxic action of neonate C. culminatus venom, highlighting limitations in snakebite treatment for this species. However, the metalloprotease inhibitor Prinomastat substantially thwarted the procoagulant venom activity, while 2,3-dimercapto-1-propanesulfonic acid (DMPS) was much less effective. These results confirm that venom-induced Factor X activation (a procoagulant action) is driven by metalloproteases, while also suggesting Prinomastat as a more promising potential adjunct treatment than DMPS for this species (with the caveat that in vivo studies are necessary to confirm this potential clinical use). Conversely, the serine protease inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) inhibited the direct fibrinogen cleaving actions of C. mictlantecuhtli venom, thereby revealing that the pseudo-procoagulant action is driven by kallikrein-type serine proteases. Thus, this differential ontogenetic variation in coagulotoxicity patterns poses intriguing questions. Our results underscore the need for further research into Mexican rattlesnake venom activity, and also highlights potential limitations of current antivenom treatments.

[Ascending aorta and aortic arch hypoplasia in a patient with connective tissue dysplasia and multiple deficit of coagulation factors]. / Gipoplaziya voskhodyashchego otdela i dugi aorty u bol'nogo s displaziei soedinitel'noi tkani i kombinirovannym defitsitom plazmennykh faktorov svertyvaniya.

Connective tissue dysplasia (CTD) is an urgent problem, especially in young and employable people. Damage to cardiovascular system and, in particular, aorta is predominant factor determining the incidence of various complications and mortality in patients with CTD. The authors report surgical treatment of aortic hypoplasia in an adolescent patient with connective tissue dysplasia syndrome and combined deficiency of coagulation factors.

Pharmacological management of rare coagulation factor deficiencies besides hemophilia.

INTRODUCTION: Rare coagulation factor deficiencies are less-known disorders with variable effects on the patient's life. Management of such patients is a challenge due to the paucity of evidence-based data, more so when patients with these rare disorders encounter a more rare, related condition, like inhibitor development or thrombosis. AREA COVERED: A comprehensive literature search related to RCFDs and management was performed in PubMed in order to discuss therapeutic options and challenges, prophylaxis, management of minor and major surgeries, obstetric and gynecological complications, inhibitor development, and thrombosis. EXPERT OPINION: Although significant changes have occurred in the management of RCFDs in recent years, more evidence-based studies besides expert opinion are needed for optimal management.

Ligneous gingivitis secondary to plasminogen deficiency: a multidisciplinary diagnostic challenge.

Plasminogen deficiency is a genetic condition resulting in deposition of extravascular fibrin within mucosal tissues. Lesions associated with plasminogen deficiency most commonly affect the eyes, while intraoral lesions, when present, affect the marginal aspects of the gingiva. We report a diagnostically challenging case of ligneous gingivitis, which developed in a young male patient in the absence of other clinical lesions. Due to the rarity of this condition, it may fall under the radar of dentists and dental specialists, leading to missed or delayed diagnosis.

Thromboelastography Reaction-Time Thresholds for Optimal Prediction of Coagulation Factor Deficiency in Trauma.

BACKGROUND: Coagulopathy is common in multitrauma patients and repletion of procoagulant factor deficiency with fresh frozen plasma (FFP) improves hemostasis. Optimal kaolin-thromboelastography thresholds for FFP transfusion in trauma patients have not been well established. STUDY DESIGN: Adult trauma patients with an Injury Severity Score ≥15 were included in this retrospective observational cohort study. The primary end point was area under the receiver operating characteristic curve (AUROC) for reaction time (R-time) to detect procoagulant factor deficiency, as reflected by an elevated international normalized ratio (INR) or aPTT. Test characteristics for the optimal R-time threshold calculated in our study were compared against thresholds recommended by the American College of Surgeons for FFP transfusion. RESULTS: Six hundred and ninety-four pairs of thromboelastography and conventional coagulation tests were performed in 550 patients, with 144 patients having additional pairs of tests after the first hour. The R-time was able to detect procoagulant factor deficiency (INR ≥1.5 AUROC 0.80; 95% CI, 0.75 to 0.85; aPTT ≥40 seconds AUROC 0.85; 95% 0.80 to 0.89) and severe procoagulant factor deficiency (INR ≥2.0 AUROC 0.82; 95% CI, 0.73 to 0.99; aPTT ≥60 seconds AUROC 0.89; 95% CI, 0.81 to 0.98) with good accuracy. Optimal thresholds to maximize sensitivity and specificity were 3.9 minutes for detection of INR ≥1.5, 4.1 minutes for detection of aPTT ≥40 seconds, 4.3 minutes for detection of INR ≥2.0, and 4.3 for detection of aPTT ≥60 seconds. Currently recommended R-time thresholds for FFP transfusion had 100% specificity for detecting procoagulant factor deficiency, but low sensitivity (3% to 7%). CONCLUSIONS: R-time can detect procoagulant factor deficiency in multitrauma patients with good accuracy, but currently recommended R-time thresholds are highly specific and not sensitive. Use of low-sensitivity thresholds might result in undertreatment of many patients with procoagulant factor deficiency.

von Willebrand Disease and other hereditary haemostatic factor deficiencies in women with a history of postpartum haemorrhage.

INTRODUCTION: Postpartum haemorrhage (PPH) is the main cause of maternal morbidity and mortality globally, but it is far more important in non-developed countries. PPH represents 25% of all maternal deaths worldwide. Women with von Willebrand disease (VWD) and other inherited haemorrhagic disorders are at increased risk of PPH. Our aim was to establish a probable association of severe PPH in women with a history of haemostatic abnormalities. METHODS: An observational, controlled study of adult women with a one or more episodes of severe PPH requiring treatment in an intensive care unit or >10 units of blood products during the 24-hour period after diagnosis and their controls. The tests performed were blood cell count, blood group, renal, viral, liver function and haemostatic tests, fibrinogen, activity of the plasma factors and specific test to diagnose and classify VWD. RESULTS: We included 124 women with 133 PPH events and their controls. The median age at the first event was 25.5 years old. Results were significantly different between the groups in terms of fibrinogen concentration, VWF:Ag, VWF:RCo and FVIII. A specific diagnosis was established in 69 (55.6) and 4 (3.2%) patients in the PPH group and controls, respectively. Of 61 patients with VWD, 57 had type 1, two had type 2A, and another two had type 2B. CONCLUSION: Our results show a relationship between PPH and inherited haemostatic disorders. VWD was the most frequent diagnosis. Appropriate and opportune diagnosis before pregnancy of inherited haemostatic disorders may be important to effectively prevent and treat PPH.

New data from the Italian National Register of Congenital Coagulopathies, 2016 Annual Survey.

BACKGROUND: In Italy, the National Register of Congenital Coagulopathies (NRCC) collects epidemiological and therapeutic data from patients affected by haemophilia A (HA), haemophilia B (HB), von Willebrand's disease (vWD) and other rare coagulation disorders. Here we present data from the 2016 annual survey. MATERIALS AND METHODS: Data are provided by the Italian Haemophilia Centres, on a voluntary basis. Information flows from every Centre to a web-based platform of the Italian Association of Haemophilia Centres, shared with the Italian National Institute of Health, in accordance with current privacy laws. Patients are classified by diagnosis, disease severity, age, gender and treatment-related complications. RESULTS: In 2016, the total number of patients with congenital coagulopathies in the NRCC was 10,360: 39.8% of these patients had HA, 31.5% had vWD, 8.5% had HB, and 20.2% had less common factor deficiencies. The overall prevalence of HA and HB was 13.9/100,000 males and 3.0/100,000 males, respectively. The overall prevalence of vWD was 5.4/100,000 inhabitants. During 2016, 126 patients had current alloantibodies to factor VIII (FVIII) or factor IX (FIX) and were under treatment with bypassing agents and/or immune tolerance induction. Overall, 388 patients with a history of alloantibodies were recorded in the NRCC of whom 337 with severe HA and 12 with severe HB. Coagulation factor use, evaluated from treatment plans, was approximately 451,000,000 IU of FVIII for HA patients (7.5 IU/inhabitant), and approximately 53,000,000 IU of FIX for HB patients (0.9 IU/inhabitant). DISCUSSION: The prevalences of HA and HB fall within the ranges reported in more developed countries; the consumption of FVIII and FIX was in line with that of other European countries (France, United Kingdom) and Canada. The NRCC, with its bleeding disorder dataset, is a helpful tool for shaping public health policies, as well as planning clinical and epidemiological research projects.

A novel combined treatment for plasminogen deficiency with lung involvement.

Plasminogen deficiency is characterized by fibrin-rich pseudomembrane formation on all mucosal surfaces, particularly the conjunctiva. Respiratory system involvement is common; fibrin often obstructs the upper or lower respiratory tract, causing death. Although many treatments have been applied, no definitive treatment (especially of the respiratory involvement) yet exists. Although excision of tracheobronchial tree membranes affords temporary improvement, this should be performed only for patients in severe respiratory distress; the procedure triggers fibrin redeposition. Here, we share our experience with an 8-year-old plasminogen-deficient female with severe lung involvement; we successfully delivered local tissue plasminogen activator followed by nebulized fresh frozen plasma.

Thrombin and plasmin generation in patients with plasminogen or plasminogen activator inhibitor type 1 deficiency.

INTRODUCTION: Deficiencies of plasminogen and plasminogen activator inhibitor type 1 (PAI-1) are rare disorders of fibrinolysis. Current laboratory assays for analysis of activity of plasminogen and PAI-1 do not provide an accurate correlation with clinical phenotype. METHODS: The Nijmegen Hemostasis Assay (NHA) was used to simultaneously measure thrombin and plasmin generation in 5 patients with plasminogen deficiency (PLGD) and 10 patients with complete PAI-1 deficiency. Parameters analysed included: lag time ratio, thrombin peak time ratio, thrombin peak height, thrombin potential (AUC), fibrin lysis time, plasmin peak height and plasmin potential. Parameters were expressed as a percentage compared to a reference value of 53 healthy normal controls. RESULTS: Patients with PLGD demonstrated a short lag time and thrombin peak time, with normal thrombin peak height but an increased AUC. Plasmin generation was able to be detected in only one (23% plasminogen activity) of the five PLGD patients. All ten PAI-1 deficient patients demonstrated a short lag and thrombin peak time, low thrombin peak height with normal AUC. Plasmin generation revealed an increased plasmin peak and plasmin potential; interestingly, there was a large variation between individual patients despite all patients having the same homozygous defect. CONCLUSION: Patients with either PLGD or PAI-1 deficiency show distinct abnormalities in plasmin and thrombin generation in the NHA. The differences observed in the propagation phase of thrombin generation may be explained by plasmin generation. These results suggest that disorders of fibrinolysis also influence coagulation and a global assay measuring both activities may better correlate with clinical outcome.

Rare clotting factor deficiency among Sudanese children.

: Rare clotting factor (F) deficiency is a deficiency of one or more of coagulation factors other than FVIII, FIX and vonWillebrand (FI, FII, FV, FV + FVIII, FVII, FIX, FX, FXI and FXIII) that cause bleeding disorders and are inherited as autosomal recessive. Descriptive study was conducted in Hemophilia Centre, Khartoum, Sudan. The medical files of pediatric patients presented to the center were reviewed retrospectively. Forty-seven patients (male : female ratio = 1.2 : 1) were included. The majority (93.6%) have parental history of consanguinity and around one third (31.9%) have family history of bleeding disorder. FV deficiency was the most common deficient factor (36.2%) followed by FI deficiency (23.4%) and FX111 deficiency (21.3%). Bruising (46.8%) and epistaxis (25.5%) were the most common presenting complains. FV deficiency mainly presented with cutaneous ecchymosis (47.1%). FI deficiency presented with umbilical bleeding (45.5%) and FXIII presented with cutaneous ecchymosis (50%). Rare clotting factor deficiency is an existing disease in Sudan with the male : female ratio was 1.2 : 1. FV deficiency, FI deficiency, FXIII deficiency were the common deficiency encountered.