scholarly journals Superwarfarin (Long-Acting Anti-coagulant Rodenticides) Poisoning: from Pathophysiology to Laboratory-Guided Clinical Management

2019 ◽  
Vol 40 (4) ◽  
pp. 175-185 ◽  
Author(s):  
Yeow-Kuan Chong ◽  
Tony Wing-Lai Mai
Keyword(s):  
Prothrombin Time ◽  
Vitamin K ◽  
Coagulation Factors ◽  
Fresh Frozen Plasma ◽  
The Body ◽  
High Dose ◽  
Fresh Frozen ◽  
History Of ◽  
K Deficiency ◽  
Long Acting

Superwarfarins are long-acting anticoagulant rodenticides developed from warfarin. The mechanism of action is by inhibition of vitamin K epoxide reductase, resulting in the inability of the body to recycle vitamin K. Deficiency of vitamin K thereafter leads to inability for the body to synthesise vitamin K-dependent coagulation factors, factor II, VII, IX, and X, leading to prolonged prothrombin time. Due to the bulky aromatic sidechains, superwarfarins have a much longer half-life when compared to warfarin, and exposure to superwarfarins results in a prolonged period of anticoagulation which can result in clinical bleeding. Diagnosis is straight forward in patients with known history of superwarfarin exposure but has proved difficult for patients who did not report superwarfarin intake. Superwarfarin poisoning should therefore be suspected in all patients with unexplained prolongation of prothrombin time, and can be confirmed by their detection in serum. Treatment for superwarfarin poisoning includes rapid correction of factor deficiencies with either four factor prothrombin complex concentrate or fresh frozen plasma in patients with active bleeding, and high dose vitamin K therapy given multiple times per day for a prolonged period of weeks to months.

scholarly journals Stability of Thawed Apheresis Fresh-Frozen Plasma Stored for up to 120 Hours at 1°C to 6°C

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
William P. Sheffield ◽  
Varsha Bhakta ◽  
Qi-Long Yi ◽  
Craig Jenkins
Keyword(s):  
Prothrombin Time ◽  
Closed System ◽  
Whole Blood ◽  
Coagulation Factors ◽  
Fresh Frozen Plasma ◽  
Refrigerated Storage ◽  
Fresh Frozen ◽  
Frozen Plasma ◽  
Over Time ◽  
Made In

Regulations concerning the storage of transfusable plasma differ internationally. In Canada, plasma obtained from whole blood donations and frozen within 24 hours of phlebotomy (frozen plasma, FP) may be thawed and transfused within 120 hours of refrigerated storage. However, plasma frozen within 8 hours of phlebotomy following apheresis donation (FFPA) must be transfused within 24 hours of thawing and refrigeration. Our objectives were to measure coagulation factors (F) V, VII, and VIII, fibrinogen activities, and the prothrombin time (PT) in thawed refrigerated FFPA at 0, 24, and 120 hours of storage and to compare these values to those in thawed refrigerated FP. Fibrinogen activity remained unchanged over time, while mean factor levels in 28 FFPA units declined by 17% (FV), 19.7% (FVII), and 54.6% (FVIII) over 120 hours, while PT values rose to 7.6%. Factor activities were significantly higher in FFPA than FP after 120 hours of refrigerated storage. Residual FVIII activities in thawed FFPA met predefined noninferiority criteria compared to thawed FP after 120 hours. These results support a change in Canadian regulations to permit transfusion of thawed FFPA made in a closed system and refrigerated for up to 120 hours, one that could reduce wastage of transfusable plasma.

scholarly journals Characteristics of Acute Transfusion Reactions and its related factors in Cipto Mangunkusumo Hospital Jakarta, Indonesia

2019 ◽  
Vol 10 (1) ◽  
pp. 15-20
Author(s):  
Pustika Amalia Wahidiyat ◽  
Elida Marpaung ◽  
Stephen Diah Iskandar
Keyword(s):  
Fresh Frozen Plasma ◽  
The Body ◽  
Moderate Degree ◽  
Related Factors ◽  
Mild Degree ◽  
Fresh Frozen ◽  
Life Threatening ◽  
History Of ◽  
Incompatibility Reactions ◽  
Transfusion Reactions

Latar belakang: Reaksi transfusi akut (RTA) merupakan sekelompok kejadian yang tidak diinginkan akibat pemberian transfusi darah. Manifestasi dari RTA bervariasi dari yang ringan hingga mengancam nyawa. Saat ini, data mengenai reaksi transfusi di Indonesia masih sangat terbatas. Dalam studi ini, kami bertujuan untuk memberikan gambaran mengenai karakteristik RTA dan faktor-faktor yang mempengaruhinya. Metode: Studi ini merupakan studi retrospektif yang melibatkan 288 subyek dengan RTA. Studi dilakukan di Rumah Sakit Dr. Cipto Mangunkusumo, dimulai sejak Januari hingga Desember 2017. RTA dikelompokkan berdasarkan sistem tubuh yang mengalami manifestasi, serta derajat manifestasinya. Hasil: Sel darah merah merupakan produk darah utama yang ditransfusikan ke subyek, diikuti dengan konsentrat trombosit, plasma segar beku, dan kriopresipitat. Lima gejala utama dari RTA adalah gatal, demam/kenaikan suhu tubuh, menggigil, urtikaria, dan angioedema. Berdasarkan sistem tubuh yang terkena, umumnya RTA bermanifestasi sebagai gejala pada kulit (56.6%). Berdasarkan derajat manifestasinya, RTA umumnya dikategorikan dalam derajat ringan (55.9%). Anak-anak cenderung mengalami manifestasi yang ringan (64.8%) dan utamanya bermanifestasi pada kulit (65.4%). Riwayat transfusi mempengaruhi derajat RTA secara signifikan. RTA derajat sedang dan gejala konstitusional lebih banyak ditemukan pada subyek yang mendapat PRC dibanding produk darah lainnya. Kesimpulan: Umumnya RTA bermanifestasi sebagai gejala dermatologi. Hanya sedikit kasus RTA yang disebabkan oleh reaksi inkompatibilitas. Manifestasi dan derajat RTA juga dipengaruhi oleh umur, riwayat transfusi, dan jenis komponen darah.  Kata kunci: Transfusi darah, reaksi transfusi akut, riwayat transfuse, usia   Abstract   Background: Acute transfusion reactions (ATRs) are a group of adverse events caused by blood transfusions. Manifestations of ATRs vary from mild to life threatening. At present, data about transfusion reactions in Indonesia are still limited. In this study, we aim to determine the characteristics of ATRs and its related factors. Methods: This was a retrospective study of 288 subjects with ATRs. The study was conducted in Cipto Mangunkusumo Hospital, started from January to December 2017. ATRs were categorized based on the body systems affected and degree of manifestations. Results: Packed red cells (PRC) was the predominant blood product (51.4%) which was transfused to subjects, followed by thrombocyte concentrate (TC), fresh frozen plasma (FFP), and cryoprecipitate. Five most common predominant symptoms of ATRs were pruritus/itch, febrile/increased temperature, chills, transient urticaria, and angioedema. Based on the affected body systems, the majority of ATRs manifested as dermatologic symptoms (56.6%). Based on the degree of manifestations, the majority of ATRs were categorized as mild degree (55.9%). Children tended to have milder symptoms (64.8%), which mostly manifested as dermatologic symptoms (65.4%). History of transfusion affected the degree of ATR significantly. Moderate degree of ATRs and constitutional symptoms were found more common in subjects who received PRC than other blood products. Conclusion: Most of ATRs manifest as dermatologic symptoms, which represent allergic reactions. Only a small portion of ATRs are caused by incompatibility reactions. The manifestation and degree of ATRs are also affected by age, history of transfusion, and type of blood components.  Keywords: Blood transfusion, acute transfusion reaction, transfusion history, age

scholarly journals Surreptitious ingestion of a long-acting vitamin K antagonist/rodenticide, brodifacoum: clinical and metabolic studies of three cases

Blood ◽  
1990 ◽  
Vol 76 (12) ◽  
pp. 2555-2559 ◽  
Author(s):  
JN Weitzel ◽  
JA Sadowski ◽  
BC Furie ◽  
R Moroose ◽  
H Kim ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Fresh Frozen Plasma ◽  
Vitamin K Antagonist ◽  
Term Therapy ◽  
Vitamin K1 ◽  
Metabolic Studies ◽  
Elimination Half ◽  
Fresh Frozen ◽  
Long Acting

Abstract The vitamin K metabolism of three patients with factitious purpura due to brodifacoum ingestion was studied. These patients, who presented with bleeding disorders due to deficiency of the vitamin K-dependent blood clotting proteins, were refractory to vitamin K1 at standard doses and required fresh frozen plasma to control bleeding until large doses of vitamin K1 were used. Metabolic studies demonstrated a blockade in vitamin K utilization, consistent with the presence of a vitamin K antagonist, but the patients denied use of anticoagulants. Warfarin assays were negative. We show that the factitious purpura in each patient was due to the surreptitious ingestion of brodifacoum, a potent second generation long-acting vitamin K antagonist used as a rodenticide. The coagulopathies responded to long-term therapy with large doses of vitamin K1. The serum elimination half-time for brodifacoum ranged from 16 to 36 days in these patients. The anticoagulant effect is of long duration, requiring chronic vitamin K treatment. With increasing availability of new rodenticides, factitious purpura due to surreptitious ingestion of these potent vitamin K antagonists is emerging as a new problem, previously associated with warfarin, with important implications for diagnosis and treatment.

Surreptitious ingestion of a long-acting vitamin K antagonist/rodenticide, brodifacoum: clinical and metabolic studies of three cases

Blood ◽  
1990 ◽  
Vol 76 (12) ◽  
pp. 2555-2559 ◽  
Author(s):  
JN Weitzel ◽  
JA Sadowski ◽  
BC Furie ◽  
R Moroose ◽  
H Kim ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Fresh Frozen Plasma ◽  
Vitamin K Antagonist ◽  
Term Therapy ◽  
Vitamin K1 ◽  
Metabolic Studies ◽  
Elimination Half ◽  
Fresh Frozen ◽  
Long Acting

The vitamin K metabolism of three patients with factitious purpura due to brodifacoum ingestion was studied. These patients, who presented with bleeding disorders due to deficiency of the vitamin K-dependent blood clotting proteins, were refractory to vitamin K1 at standard doses and required fresh frozen plasma to control bleeding until large doses of vitamin K1 were used. Metabolic studies demonstrated a blockade in vitamin K utilization, consistent with the presence of a vitamin K antagonist, but the patients denied use of anticoagulants. Warfarin assays were negative. We show that the factitious purpura in each patient was due to the surreptitious ingestion of brodifacoum, a potent second generation long-acting vitamin K antagonist used as a rodenticide. The coagulopathies responded to long-term therapy with large doses of vitamin K1. The serum elimination half-time for brodifacoum ranged from 16 to 36 days in these patients. The anticoagulant effect is of long duration, requiring chronic vitamin K treatment. With increasing availability of new rodenticides, factitious purpura due to surreptitious ingestion of these potent vitamin K antagonists is emerging as a new problem, previously associated with warfarin, with important implications for diagnosis and treatment.

Congenital Deficiency of Vitamin K-Dependent Coagulation Factors and Protein C

1984 ◽  
Vol 51 (03) ◽  
pp. 343-346 ◽  
Author(s):  
V Vicente ◽  
R Maia ◽  
I Alberca ◽  
G P T Tamagnim ◽  
A Lopez Borrasca
Keyword(s):  
Vitamin K ◽  
Protein C ◽  
Coagulation Factors ◽  
Vitamin K3 ◽  
Congenital Deficiency ◽  
History Of ◽  
K Deficiency ◽  
Dependent Protein ◽  
Fresh Plasma ◽  
Intravenous Vitamin

SummaryA 15-month-old girl from Coimbra (Portugal) had a history of numerous hemorrhagic episodes with multiple bruises, hematomas but not hemarthroses. On serial testing she showed deficiency of factors II, VII, IX, X and protein C. Malabsorption- induced vitamin K deficiency, liver disease or ingestion of a coumarin compound were excluded. An absence of detectable abnormalities was found among her relatives. Consanguinity was not present. The immunologic assay, immunoelectrophoresis or antibody neutralization, revealed much higher levels of these factors than the clotting assay. The non-physiological activator (Echis carinatus venom) produced higher levels of prothrombin activation than those detected by physiological activation. Twodimensional immunoelectrophoresis of the patient’s plasma in calcium showed that prothrombin had the same mobility as acarboxyprothrombin. No significant response to large doses of intravenous vitamin K3 (6 mg) was observed. Transfusion of 120 ml of frozen fresh plasma led to an immediate increase in the procoagulant activities of vitamin K dependent protein, similar to that found after perfusion of plasma plus vitamin K3. The results obtained from this patient suggest a defect in the gammacarboxylation mechanism inside the hepatocyte.

Management of Excessive Anticoagulant Effect Due to Vitamin K Antagonists

Hematology ◽  
2008 ◽  
Vol 2008 (1) ◽  
pp. 266-270 ◽  
Author(s):  
Francesco Dentali ◽  
Mark A. Crowther
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Coagulation Factor ◽  
Reference Interval ◽  
Coagulation Factors ◽  
Fresh Frozen Plasma ◽  
Treatment Modalities ◽  
Oral Vitamin ◽  
Fresh Frozen ◽  
Frozen Plasma

Abstract Unexpectedly elevated INR values are commonly encountered in clinical practice. In the absence of bleeding, such values may be treated with either simple warfarin withdrawal or the administration of low doses of oral vitamin K. Oral vitamin K will more rapidly return the INR to the therapeutic reference interval; however, its impact on bleeding is unknown. If the INR is in excess of 10, most experts would recommend the administration of vitamin K and, in the case of active bleeding, additional administration of coagulation factors either in the form of fresh frozen plasma (FFP) or prothrombin complex concentrates (PCC). Coagulation factor replacement is required given the need to urgently correct the INR; however, vitamin K should not be forgotten since it is required to antagonize the effect of warfarin, preventing “rebound” anticoagulation after transfused coagulation factors are consumed. This paper will review the evidence supporting various treatment modalities and will provide suggestions for treatment. Future advances in this area will likely focus on evaluations of the relative merits of FFP and PCCs.

scholarly journals Hereditary disorders of blood coagulation factors amongst Jews!

2020 ◽  
Vol 5 (3) ◽  
pp. 01-01
Author(s):  
Hilary Solomons
Keyword(s):  
Factor Viii ◽  
Prothrombin Time ◽  
Blood Coagulation ◽  
Coagulation Factors ◽  
Fresh Frozen Plasma ◽  
Ashkenazi Jews ◽  
Blood Coagulation Factors ◽  
Fresh Frozen ◽  
Hereditary Disorders ◽  
Frozen Plasma

This is picked up on routine bloods such as partial thromboplastin times. The prothrombin time is usually normal. There is no excess bleeding after trauma. They may however still bleed excessively after surgery. In terms of treatment or therapy the factor XI level must be kept at greater than 30 % with fresh frozen plasma 5-20 ml./kg./ day. The inheritance is autosomal recessive.In Israel the incidence is 8% amongst Ashkenazi Jews. FactorXI deficiency is also known as; Rosenthal Syndrome or Haemophilia C. Sometimes the child may bleed excessively e.g. at circumcision but they do not bleed as severely as haemophiliacs (factor VIII deficiency) and rarely present with haemarthroses. Haemorrhage is usually from mucousal surfaces.

Spectrophotometric Assays of Prothrombin in Plasma of Patients Using Oral Anticoagulants

1979 ◽  
Vol 42 (04) ◽  
pp. 1296-1305 ◽  
Author(s):  
R M Bertina ◽  
W van der Marel-van Nieuwkoop ◽  
E A Loeliger
Keyword(s):  
Prothrombin Time ◽  
Vitamin K ◽  
Oral Anticoagulation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Factor V ◽  
Anticoagulant Treatment ◽  
Factor Ii ◽  
K Deficiency

SummaryTwo spectrophotometric assays for prothrombin have been developed and compared with a one stage coagulant and an immunological assay. One of these assays (called the XAPC assay) uses a combination of factor Xa, phospholipid, Ca2+ and factor V as activator of prothrombin, and measures only normal prothrombin. The second (the ECAR assay) uses Echis carinatus venom as activator. This assay measures both normal prothrombin and PIVKA II (protein induced by vitamin K antagonists/absence). Combination of the results obtained by the XAPC and ECAR assays provides rapid and reliable information on the degree of “subcarboxylation” of prothrombin (oral anticoagulation, vitamin K deficiency).For patients on long term anticoagulant treatment the prothrombin time (Thrombotest) shows better correlation with the ratio prothrombin/prothrombin plus PIVKA II (XAPC/ ECAR) than with the factor II concentration. For patients starting the anticoagulant treatment there is no correlation between the Thrombotest time and the XAPC/ECAR ratio.It seems doubtful that (a) spectrophotometric factor II assay(s) will be as useful as the prothrombin time in the control of oral anticoagulation.

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