Case report 1

A 60-year-old male patient, blind, was transferred to hospital with a diagnosis of mediastinal mass found during chest X-ray. During examination all clinical and laboratory signs of Vitamin K – dependent coagulopathy were diagnosed. Clinical interview concluded that the patient found by touch and was self-administered the tablets of Neodicumarinum (VKA from the group of coumarins). The tablets were prescribed to his wife for thrombophlebitis. He had confused these tablets with the nitrates prescribed to him. The hemorrhagic coagulopathy was stopped by the administration of Prothrombin Complex Concentrate and preparation of vitamin K. The mediastinal “mass” entirely resolved. In conclusion the hemo-mediastinum was diagnosed as tumor, mis-diagnosing the hemorrhagic syndrome signs.

Case report 2

The patient K., 45, was hospitalized at the Amur Regional Clinical Hospital on 04.10.2011, due to massive sub dermal and endermic hematomas, bleeding gums and nasal bleeding. The patient reported that he had originally noticed skin hematomas and nasal and dermal bleedings in June, 2010. He was hospitalized at the therapeutic department of the city hospital where increased A-PPT up to 62.5 s was found (physiological range up to 35 s), a prolongation of the prothrombin time to 45.5 s and INR = 6. The coagulation was not studied in more details. The reason of coagulation failed to be determined: the patient categorically denied the administration of indirect anticoagulants; hepatic pathology, gall-bladder pathology and pathology of the intestinal tract were excluded. “DIC-syndrome of unknown etiology” was diagnosed. The patient received transfusions of fresh frozen plasma. It quickly led to the amelioration of the hemorrhagic syndrome and to the normalization of the coagulogram indexes. In 2 weeks the patient was dismissed from the hospital without signs of hemorrhagic syndrome. At the end of September 2011, the patient noticed again nasal bleeding. In early October the patient was admitted to the hematology department because of progressive multiple hematomas on the limbs and body. During careful questioning, the patient categorically denied the administration of any medicinal drug influencing the blood coagulation system. The patient reported diabetes mellitus type II during the last 5 years and respective treatment with Protaphane, 10 units in the morning and 10 units in the evening, with a background of suitable diet. During the examination of the liver, gall-bladder, gastro-intestinal tract and kidneys, no pathologies were found. The patient categorically denied being beaten (taking into account the location of the hematomas). The clinical blood analysis revealed anaemia (hemoglobulin – 103 g/dl) and erythrocyte sedimentation rate (ESR) of 35 mm/h. According to myelogram, hemablastosis was excluded. The coagulogram assessment revealed the following: ➢ rapid deceleration of I-II phases of the extrinsic blood coagulation ➢ deficiency of the factors of the prothrombin complex – prolongation of the echitoxic time (II factor), lebetoxic time (X factor) and prothrombin time (VII factor) ➢ decreased factor IX ➢ % V, VII, XI factors was not changed ➢ the formation of prothrombinase through the intrinsic coagulation pathway was not affected ➢ the final stage of coagulation was normal ➢ moderate hyperfibrinogenemia ➢ the activity of Antithrombin III and plasminogen was satisfactory ➢ low level of protein C (its synthesis also depends upon Vitamin K). Therefore deficiency of Vitamin K-dependent factors of coagulation and of the inhibitor of coagulation protein C was diagnosed. The patient was further interviewed with the purpose of diagnosing the possible reasons (including criminal reasons) of the severe deficiency of K-dependent factors. To the question about rat-poison use, the patient’s answer was affirmative. From March to June 2011 and from July to September 2011, the patient, a greengrocer, without any professional help and with bare hands used rat-poison in large quantities. The active agent in rat-poison was brodifacoum. The patient reported that he had worked in a closed room, the food-store, and that he consumed himself fruit and vegetables kept in this location. Therefore, brodifacoum poisoning was diagnosed. Upon treatment start with fresh frozen plasma and 1% Vikasolum solution, 1 ml 3 times a day intravenously, the hemorrhagic syndrome recessed in 3 days. During the following month the hemorrhagic syndrome was completely resolved (with the administration of Vikasolum p.o.). Coagulogram indices normalized at the beginning of the second month.

Case report 3

A female patient, aged 60, was repeatedly admitted to different hematology units in Moscow, with severe hemorrhagic syndrome for several years. The huge bruises were noticed on the upper skin, except from areas difficult to approach by patient’s hands (the area of the vertebral spine). The round, smooth, painful lesions were palpated in the abdominal cavity (subserosal-haematomas of the intestine) and hematuria was present. All laboratory results of Vitamin K-dependent coagulopathy were present. The calm behavior of the patient, in spite of emergency of the situation as depicted by the medical personnel, made the doctor suspicious. The patient was hospitalized to the intensive care unit without clothes. When the patient’s clothes were examined, a unit package of neo-dicoumarin was discovered. The therapy with quarantine fresh frozen plasma and Vitamin K preparation led to clinical recovery and normalization of the laboratory results. During conversation with the patient, the attending physician let her know that the medical personnel had recognized the cause of her illness and she was recommended psychiatrist assistance.

Case report 4

A female patient, aged 54 years, visited doctors for several years because of bruises and hematuria. She was treated repeatedly in the haematology units of the city hospitals in Moscow. During the latest admission, huge “bruises” were observed on the mammary gland skin and on the femora skin. During the examination of her clothes, they found a package of neo-dicoumarin. The treatment with quarantine fresh frozen plasma and Vitamin K-preparations stopped the hemorrhagic syndrome and normalized the coagulogram. The doctor explained delicately the reason of her disease. She was recommended to stop using the dangerous medicinal drugs and to visit a psychiatrist.

Case report 5

The patient M, aged 53 years, was admitted to the hematology unit of Amur Regional Clinical Hospital from the district of Amur region with the provisional diagnosis “Hemophilia B”. He complained of “reasonless” bruises on his skin, recidivating nasal bleedings and urine discoloration (the color of the meat slops). He considered himself ill since June 3, 2012, when he first noticed the nasal bleeding, urine with blood mixture, in sort of meat “slops”, hematomas on his lower limbs. The symptomatic therapy was administered and the patient was transferred to the regional hospital. The blood test revealed a moderate post hemorrhagic anemia (erythrocytes 2.8 × 10 12 /l, hemoglobulin 72 g/dl). Erythrocytes abundance was observed in the urine. Coagulogram revealed hypo-coagulation (after performing clotting time according to Louis White, INR, prothrombin time, APPT). A more detailed coagulogram was not done. It was not possible to determine the etiology of such coagulation. After the transfusion with fresh frozen plasma, the nasal bleeding and nephritic bleeding stopped. The results of the coagulogram tests normalized. The physicians reached a diagnosis of DIC-syndrome of undefined etiology. The patient was discharged from the hospital on 4.07.12 with improvement of his condition; the nasal bleedings and the hemorrhagic syndrome were absent. After 10 days the clinical picture of the hemorrhagic syndrome developed again on the skin and nasal and nephritic bleedings resumed. On 23.07.12 the patient came to the Amur Advisory Clinic. The coagulogram’s analysis revealed the increase of APPT to 60 s., PTI – 40 s., INR to 5.3 and decrease of IX blood coagulation factor (Christmas factor). He was sent to the hematology unit with the provisional diagnosis “Hemophilia B”. The elderly age of the patient, absence of hereditary history, high tolerability of the physical activity, absence of the obvious bleeding from the traumas, INR increase allowed to exclude immediately the diagnosis Hemophilia B. In the hematology unit of the Amur Regional Clinical Hospital an expanded coagulogram was firstly asked. The coagulogram conclusion was the following: rapid deceleration of I-II phases of extrinsic blood coagulation; factor deficiency of prothrombin-converting complex – the prolongation of the echitox time (II factor), lebetox time (X factor) and prothrombin time (VII factor), the quantity of factor IX was decreased; the percentage composition of factors V, VIII, XI was within normal limits; the formation of prothrombinase on the intrinsic coagulation pathway was not damaged; the final stage of coagulation was in the norm; the activity of antithrombin III and plasminogen was satisfactory; a low level of protein C. It was diagnosed the deficiency of Vitamin K-dependent factors of coagulation and coagulations inhibitor protein C. A light severe anemia was observed (hemoglobulin – 102 GM/DL; erythrocytes 3.2 × 10 9 /l; leucocytes – 9.2 × 10 9 /l, thrombocytes -250 × 10 9 /l). According to the myelogram, hemablastosis was excluded. The biochemical analysis of the blood was within normal limits. There were erythrocytes throughout the urine. According to all these results vitamin K-dependent coagulopathy was diagnosed. The thorough questioning of the patient about possible reasons of coagulopathy including criminal motives did not lead to positive results, the patient categorically refused to admit VKA consumption and work with any rat-poison. At liver, gastro-intestinal tract and kidneys examination, pathology associated with the said coagulopathy was not revealed. A good clinical course was achieved with the use of PCC (Protromplex 600) and Vitamin K preparations. On the third day of the treatment, the nasal and nephritic bleedings stopped, new hematomas stopped occurring on the skin. After a month the hemorrhagic syndrome completely ended (on the background of administration of Vitamin K) and coagulogram indices normalized. The patient was discharged but physicians recorded his place of residence. As it was found out later, the coagulopathy had criminal origin. One of his relatives added rodenticide containing brodifacoum into the patient’s meal.