Plasma Protein Function in Hemostasis
Genesio Murano, Rodger L. Bick in Basic Concepts of Hemostasis and Thrombosis, 2019
There exist in human plasma multiple forms of an alpha globulin known as kininogen. Two major classes have been identified and are termed: low molecular weight (LMW) kininogen and high molecular weight (HMW) kininogen.145-147 The latter is “Fitzgerald or Flaujeac, or Williams factor”. Its molecular weight is about 120,000, and it functions in the activation of Factor XII.89,90,148-151 The proteolytic enzyme kal-likrein (which exists in plasma as an inactive precursor—prekallikrein), with a molecular weight of about 85,000 daltons, has the property of splitting off biologically active polypeptide fragments, preferentially from HMW kininogen.117,129,148 These fragments, known generically as kinins129,143,144 (among them the nonapeptide bradykinin), enhance vascular permeability, dilate certain blood vessels—resulting in hypotension, contract certain smooth muscles, and, perhaps, bring about the migration of leukocytes in extravascular space. 129,148,152 In addition, as pointed out earlier, kallikrein also activates Factor XII. 17,88,89 Once again, we return to Factor XII.
Benzene Carcinogenecity
Muzaffer Aksoy in Benzene Carcinogenicity, 2017
Case 56, a 43-year-old Turkish Jew, owner of a wallpaper printing shop in Istanbul had been seen by an internist because of cardiac complaints. The results of EKG were normal. There was no lymphadenopathy and hepatosplenomegaly. Hematologic data: Hb 14.3 g/dl, RBC 4.8 x 109, PCV 0.45/l, platelet 380 X 109/l, WBC 29 x 109/l with 3% band forms, 25% polymorphonuclear neutrophils, 2% monocytes, 2% eosinophiles, and 68% lymphocytes. There were numerous Gumprecht shadows in the blood film. The findings of bone marrow were consistent with the diagnosis of chronic lymphoid leukemia. Serum electrophoresis showed albumin 59.4%, alpha-1 globulin 2.2%, alpha-2 globulin 9.9%, betaglobulin 12.7%, and gamma globulin 15.8%.
Syndromes Associated with Hyperfibrino(GENO)Lysis
Rodger L. Bick in Disseminated Intravascular Coagulation and Related Syndromes, 2019
As liver disease becomes “end stage” there may also be decreased synthesis of Factors V and VIII. Early in the clinical course of chronic liver disease these two factors may actually be elevated. Synthesis of prekallikrein is also decreased; however, the clinical significance of this defect, if any, remains unclear. Patients with chronic liver disease of any etiology usually demonstrate significantly decreased levels of antithrombin III; the pathophysiology of this remains unclear and may represent either a true decreased synthesis or the synthesis of a dysfunctional antithrombin III protein.103,104 Some patients may have normal or high antithrombin III levels, since this alpha-2-globulin, like fibrinogen, may also behave as an acute phase reactant. The clinical significance of antithrombin III findings in chronic liver disease remain unclear with respect to clinical development of hypercoagulability or thrombosis.
A case report of recurrent Well’s syndrome masquerading as cellulitis
Published in Journal of Community Hospital Internal Medicine Perspectives, 2021
Anum Qureshi, Jasmine Manley, Tristan Flack, Mark H. Lowitt
Two weeks after completing glucocorticoid therapy, she returned to the emergency department with complaints of severe back pain as well as recurrent cellulitis (lower extremities, groin, and perianal) with lower extremity edema. Significant laboratory findings included eosinophilia (11%). ANA, immunoglobulin panels, inflammatory markers, chemistries, and flow cytometry were normal. Serum protein electrophoresis revealed an elevated alpha-2 globulin fraction, but no monoclonality. She was again treated with parenteral then oral corticosteroids. Back pain was attributed to a musculoskeletal cause. Hematology and rheumatology consultants found no underlying abnormalities that could be associated with Well’s syndrome. Prednisone was again tapered over weeks, and she declined additional possible steroid sparing agents. She was free of active disease for fivemonths. Five months, later she had trauma to the left arm that led to severe arm redness, bruising and skin tear [Figure 4(a)] that initially healed, but later, she developed severe pain, redness at the site of injury (Figure 4(b)) and her symptoms were similar to the previous WS flare; she was treated with steroid and symptoms improved significantly and successfully tapered off steroids in fourweeks.
Investigational plasma kallikrein inhibitors for the treatment of diabetic macular edema: an expert assessment
Published in Expert Opinion on Investigational Drugs, 2020
Ashay D. Bhatwadekar, Viral S. Kansara, Thomas A. Ciulla
Plasma kallikrein is a serine protease synthesized mainly in the liver as a proenzyme prekallikrein (PK). The mRNA for plasma kallikrein or PK is expressed in a variety of tissues such as the brain, heart, lung, kidneys, adrenal glands, pancreas, spleen, prostate glands, and ovaries. PK is also known as the Fletcher factor due to its involvement in the fletcher trait, a condition with markedly prolonged activated partial thromboplastin time (aPTT). PK is encoded by a single gene localized on a q34-q35 region of the long arm of chromosome 4 [32]. PK is a single chain gamma-globulin zymogen with a molecular weight of 85–88 kDa, and a plasma concentration of ~490 nM. The N terminal region of PK consists of four contagious repeats composed of 4 groups of 90–91 amino acids arranged in ‘apple domains’ (A1-A4), Figure 1. The N-terminal of the PK lacks intrinsic activity and mainly involved in the recruitment of certain proteins [33]. The majority of PK circulates in plasma as a complex with alpha globulin, high molecular weight kininogen (HK). The apple domains, A1 and A4, serve as binding sites for HK. The proteolytic processing of PK leads to activated plasma kallikrein via activated factor XII (αFXIIa) on the negatively charged surface, factor XII fragment (βFXIIa) in the fluid phase and prolycarboxypeptidase on endothelial cells. Plasma kallikrein then cleaves HK to liberate bradykinin. While bradykinin directly activates the B2 receptor, the cleavage of bradykinin by carboxypeptidase generates des-arg9 bradykinin (DABK) leads to activation of B1 receptors (Figure 2).
Amyloid cardiomyopathy: a hidden heart failure cause that is often misdiagnosed
Published in Acta Clinica Belgica, 2018
Yale Tung-Chen, Miguel-Ángel Arnau
During the following days, laboratory results came up, showing ESR 9 mm/h [normal: 1–7], CRP 4 mg/dL [0–5], TSH 1.346 mU/L [0.4–4.0], D-dimer 242 ng/mL [<500], NT pro-BNP 2617 pg/mL [<400]. Serum protein electrophoresis (albumin 3.70 g/dL [3.3–5.7], alpha-1 globulin 0.23 [0.1–0.4], alpha-2 globulin 0.49 g/dL [0.3–0.9], beta globulin 1.4 g/dL [0.7–1.5], gamma globulin 1.5 g/dL [0.5–1.4]), serum immunofixation, Immunoglobulins (IgA 214 mg/dL [70–400], IgM 79 mg/dL [40–230], IgG 1,200 mg/dL [700–1,600]), and free light chain assay (Kappa 20.8 mg/L [3.3–19.4], Lambda 23.1 mg/L [5.7–26.3], ratio 0.90 [0.26–1.65]) were unremarkable. No proteinuria, urinary free light chain excretion, and immunofixation were detected. The rest of laboratory tests were normal.
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