scholarly journals Prekallikrein and high molecular weight kininogen deficiency in Oman: a challenging diagnosis in mucosal bleeding

2019 ◽  
Vol 7 (1) ◽  
pp. 11-15
Author(s):  
Hanan F Nazir ◽  
Anil V Pathare
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Coagulation Factors ◽  
Hashimoto Thyroiditis ◽  
Coagulation Cascade ◽  
High Molecular Weight Kininogen ◽  
Intrinsic Pathway ◽  
Diagnostic Challenge ◽  
Symptomatic Case ◽  
Mucosal Bleeding

Background: Prekallikrein (PK) and high molecular weight kininogen (HMWK) are contact factors that are involved in the intrinsic pathway of the coagulation cascade. Deficiency of PK or HMWK are known to be associated with prolonged a PTT, but no clinical bleeding. However, rare cases of PK deficiency have been reported to be associated with mucosal bleeding. Objective: To report on epidemiological and clinical characteristics of Omani patients with PK and HMWK deficiency, focusing on one symptomatic case. Patients and methods: We reviewed the files of Omani patients who had persistently prolonged a PTT that proved to be secondary to PK or HMWK deficiency over a period of ten years. Results: Eight cases (three with PK, five with HMWK deficiency) were identified. All but one case were asymptomatic. A thirteen year-old female with Hashimoto thyroiditis who presented with easy bruising, severe prepubertal vaginal bleeding and recurrent hematemesis proved to have prekallikrein deficiency. Acquired vWD, coagulation factors deficiency, lupus anticoagulant, platelet dysfunction were ruled out. No local cause of bleeding could be identified even after four endoscopic examinations, Meckel’s diverticulum scintigraphy and CT angiography of the abdomen. Conclusion: PK and HMWK are underestimated in Oman. Most cases were incidentally detected. They significantly impact medical costs, related to extensive laboratory testing and undue delay in planned surgical procedures. Some cases with clinical bleeding impose a diagnostic challenge.

A Case of Prekallikrein Deficiency in a Pediatric Patient.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4100-4100 ◽  
Author(s):  
Shannon L. Carpenter ◽  
Howard A. Britton
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Attention Deficit Disorder ◽  
Active Form ◽  
Coagulation Cascade ◽  
Treatment Center ◽  
Factor Xii ◽  
Thrombin Time ◽  
High Molecular Weight Kininogen ◽  
Prolonged Aptt

Abstract Prekallikrein (also known as Fletcher factor) is described as one of the contact factors, and when converted to its active form, kallikrein, is responsible for the activation of factor XII and initiation of the intrinsic pathway of the coagulation cascade. Kallikrein also converts high-molecular-weight kininogen to bradykinin, which acts as a potent vasodilator. Deficiency of prekallikrein was first described in 1965 as an autosomal recessive disorder. Hereditary deficiency of prekallikrein is not associated with a clinical bleeding disorder, but does result in a prolonged activated partial thromboplastin time (aPTT). Most cases of prekallikrein deficiency are identified through routine screening. We present a young man who was referred to our Hemophilia and Thrombophilia Treatment Center for a significantly prolonged aPTT and subsequently found to have prekallikrein deficiency. NP is a 7 year-old boy who was found to have an aPTT of 209.6 seconds on pre-operative evaluation for PE tubes and adenoidectomy. Prothrombin time (PT) was normal at 14.7 seconds, with an INR of 1.2. There was no personal or family history of bleeding. Past medical history did include bipolar disorder and attention deficit disorder, for which the patient was taking olanzapine and depakote. A 1:1 mixing study with normal plasma led to complete correction of the aPTT to 28.9 sesconds. Levels of factors VIII, IX, XI, and XII were normal at 98%, 92%, 99% and 129%, respectively. High molecular weight kininogen level was also normal. Thrombin time was normal at 17.1 sec. An incubated aPTT was performed over 3 hours with decrease in the aPTT from 179 seconds to 72 seconds, a phenomenon that has been reported previously, and is thought to be due to auto-activation of factor XII. Prekallikrein was measured at less that 15% (normal reference 55–207%). The patient subsequently underwent adeno-tonsillectomy without any excessive bleeding. This case serves as another example of the benign causes for a prolonged aPTT in the pre-operative setting in addition to those such as lupus anticoagulant or factor XII deficiency. Deficiency of prekallikrein should be included in the differential diagnosis of a prolonged aPTT, particularly in the absence of bleeding symptoms.

scholarly journals High Molecular Weight Kininogen: A Review of the Structural Literature

2021 ◽  
Vol 22 (24) ◽  
pp. 13370
Author(s):  
Michał B. Ponczek
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Thrombin Generation ◽  
Structural Investigation ◽  
Atomic Level ◽  
Structural Studies ◽  
High Molecular Weight Kininogen ◽  
Intrinsic Pathway ◽  
Cryo Electron Microscopy ◽  
Structure Of Proteins

Kininogens are multidomain glycoproteins found in the blood of most vertebrates. High molecular weight kininogen demonstrate both carrier and co-factor activity as part of the intrinsic pathway of coagulation, leading to thrombin generation. Kininogens are the source of the vasoactive nonapeptide bradykinin. To date, attempts to crystallize kininogen have failed, and very little is known about the shape of kininogen at an atomic level. New advancements in the field of cryo-electron microscopy (cryoEM) have enabled researchers to crack the structure of proteins that has been refractory to traditional crystallography techniques. High molecular weight kininogen is a good candidate for structural investigation by cryoEM. The goal of this review is to summarize the findings of kininogen structural studies.

Factor XI and Protection of the Fibrin Clot against Lysis – a Role for the Intrinsic Pathway of Coagulation in Fibrinolysis

1998 ◽  
Vol 80 (07) ◽  
pp. 24-27 ◽  
Author(s):  
Peter von dem Borne ◽  
Joost Meijers ◽  
Bonno Bouma
Keyword(s):  
Molecular Weight ◽  
Blood Coagulation ◽  
High Molecular Weight ◽  
Fibrin Clot ◽  
Contact System ◽  
Activate Factor ◽  
Factor Xii ◽  
High Molecular Weight Kininogen ◽  
Intrinsic Pathway ◽  
Factor Xi

IntroducationBlood coagulation is an important mechanism that maintains the integrity of the vascular system to prevent blood loss after injury. The conceptions on the working mechanism of coagulation are based on the waterfall or cascade model, which was already proposed more than 30 years ago, independently by Davie and Ratnoff (1) and MacFarlane (2). Blood coagulation was viewed as a series of linked proteolytic reactions in which zymogens are converted into serine proteases, ultimately leading to the formation of thrombin, which converts soluble fibrinogen into insoluble fibrin. Coagulation was thought to proceed via two pathways, an extrinsic and an intrinsic pathway. Activation of the extrinsic pathway of coagulation occurs by the exposition of tissue factor at the site of injury (3) whereas the intrinsic system is activated after exposure of plasma to an activating surface. Although the in vivo activating surface is unknown, the contact system was believed to play a role in the initiation of the intrinsic pathway. This system consists of factor XII, prekallikrein, high molecular weight kininogen and factor XI. The physiological relevance of the contact system is unclear, since a deficiency of factor XII, prekallikrein or high molecular weight kininogen does not result in a bleeding disorder. In contrast, patients deficient in factor XI, most common among Ashkenazi Jews, do suffer from variable bleeding abnormalities especially from tissues with high local fibrinolytic activity (urinary tract, nose, oral cavity, tonsils) (4, 5). This suggested there was an alternative route for the activation of factor XI, and recently such a route was described (6, 7). Thrombin was found to activate factor XI, even in the absence of a negatively charged surface (6-11), and factor XI was shown to play a role in the protection of the fibrin clot against lysis (9). In plasma the possibility cannot be excluded that the activation of factor XI by thrombin takes place via an intermediary component. Recently, it was shown that meizothrombin was capable of activating factor XI (12).

The Contact Phase of Blood Coagulation in Diabetes Mellitus and in Patients with Vasculopathy

1984 ◽  
Vol 52 (03) ◽  
pp. 221-223 ◽  
Author(s):  
M Christe ◽  
P Gattlen ◽  
J Fritschi ◽  
B Lämmle ◽  
W Berger ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Weight ◽  
Blood Coagulation ◽  
High Molecular Weight ◽  
Negative Correlation ◽  
Factor Xii ◽  
C1 Inhibitor ◽  
High Molecular Weight Kininogen ◽  
Contact Phase ◽  
Α2 Macroglobulin

SummaryThe contact phase has been studied in diabetics and patients with macroangiopathy. Factor XII and high molecular weight kininogen (HMWK) are normal. C1-inhibitor and also α2-macroglobulin are significantly elevated in diabetics with complications, for α1-macroglobulin especially in patients with nephropathy, 137.5% ± 36.0 (p <0.001). C1-inhibitor is also increased in vasculopathy without diabetes 113.2 ± 22.1 (p <0.01).Prekallikrein (PK) is increased in all patients’ groups (Table 2) as compared to normals. PK is particularly high (134% ± 32) in 5 diabetics without macroangiopathy but with sensomotor neuropathy. This difference is remarkable because of the older age of diabetics and the negative correlation of PK with age in normals.

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