OBJECTIVE: To explore the relationship between clinical features, peripheral blood cell count, coagulation function, gene mutation and hemorrhagic events and thrombotic events in essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis(PMF) patients. METHODS: Clinical data of 78 patients with ET, PV, and PMF who were admitted to the Second Affiliated Hospital of Chongqing Medical University between September 2019 and August 2020 were retrospectively analyzed. Information about sex, age, gene mutation, peripheral blood cell count, coagulation function, and hemorrhagic and thrombotic events was included, and the influence of these data on the occurrence of hemorrhagic and thrombotic events was estimated. RESULTS: Among the 78 patients with myeloproliferative neoplasms, there were 47 cases of ET, 15 cases of PV, and 16 cases of PMF.A total of 10 patients (12.82%) experienced hemorrhagic events and 27 (34.62%) experienced thrombotic events. Male,patients aged ≥ 60 years, and patients with a JAK2V617F mutation were more likely to experience thrombotic events (P<0.05). Patients with thrombotic events had higher platelet (PLT) counts and fibrinogen (FIB) levels than patients without hemorrhagic-thrombotic events (P<0.05).White blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (HGB) level, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and international normalized ratio (INR) showed no statistical difference between patients with thrombotic events and patients without hemorrhagic-thrombotic events (P>0.05). There was also no significant difference in the above-mentioned indexes between patients with hemorrhagic events and patients without hemorrhagic-thrombotic events (P>0.05). Among JAK2V617F positive myeloproliferative neoplasm patients, male patients were more likely to have thrombotic events (P<0.05), and patients with thrombotic events had higher platelet counts than those without hemorrhagic-thrombotic events (P<0.05). There was no significant difference in age, white blood cell count, red blood cell count, hemoglobin level, PT, APTT, FIB, TT or INR between patients with thrombotic events and patients without hemorrhagic-thrombotic events (P>0.05). CONCLUSION Sex, age, JAK2V617F mutation and platelet count have a certain value for predicting thrombosis in patients with myeloproliferative neoplasms.
Hemoglobins/genetics* ; Hemorrhage ; Humans ; Janus Kinase 2/genetics* ; Male ; Mutation ; Myeloproliferative Disorders/genetics* ; Polycythemia Vera/genetics* ; Retrospective Studies ; Thrombocythemia, Essential ; Thrombosis

Classical myeloproliferative neoplasm (MPN) related thrombosis mainly affects elderly patients and often involves arterial circulation, while, MPN-visceral venous thrombosis (SVT) mainly affects young women, and is closely associated with JAK2V617F mutation but not closely with CALR mutation. The pathogenesis of MPN-SVT is not only related to JAK2V617F mutation and vascular endothelial damage, but also needs further research to determine the machanism. JAK2V617F mutation is the most common in MPN-SVT clinically. Patients with non-cirrhotic SVT need to detect MPN mutation, while the detection of CALR or MPL mutation needs to be combined with clinical judgment. At present, the main treatment strategies of MPN-SVT are JAK inhibitors, supplementation of anticoagulants and treatment of portal hypertension. This article reviews the latest research progress on the epidemiology, pathogenesis, diagnosis and treatment strategies of MPN-SVT.
Aged ; Anticoagulants ; Female ; Humans ; Janus Kinase 2/genetics* ; Janus Kinase Inhibitors ; Mutation ; Myeloproliferative Disorders/genetics* ; Neoplasms ; Thrombosis ; Venous Thrombosis

OBJECTIVE: To test the anticoagulation functions, perform the genetic diagnosis and analyze the clinical characteristics in a family with combined heterozygous genetic variants of PROC and PROS1. METHODS: Peripheral blood was collected from all the family members. Hematological phenotypes and activity of anticoagulant factors were analyzed. Target genes were amplified by PCR from DNA isolated from peripheral blood, and then were analyzed by Sanger DNA sequencing. RESULTS: Many members in the family displayed the combined genetic variants in protein C and protein S, and six family members accompanied by deep venous thrombosis (DVT). The influences of genetic and secondary factors on the incidence of venous thrombosis in the family members were analyzed. The results showed that in this family, carriers of combined protein C and protein S gene defects had a higher incidence of VTE, but acquired factors still played a key role in the eventual thrombotic symptoms. CONCLUSION Venous thromboembolism (VTE) is a multifactorial disease, the combined genetic heterozygous mutations of protein C and S is an important genetic factor, and the clinical phenotype show a high heterogenicity, the secondary factors contribute to the VTE incidence.
Heterozygote ; Humans ; Mutation ; Protein C/genetics* ; Protein S/genetics* ; Risk Factors ; Venous Thromboembolism ; Venous Thrombosis/genetics*

OBJECTIVE: To investigate the overview of thrombosis in myeloproliferative neoplasms(MPN) patients, and to explore the risk factors of thrombosis at diagnosis and during follow-up. METHODS: The clinical data of 388 MPN patients treated in our hospital were collected. The patients were followed up by outpatient and phone. The risk factors of thrombosis were analyzed by statistical methods. RESULTS: Among 388 MPN patients, 161 patients (41.49%) showed thromboses at diagnosis or during follow-up. Among them, 92.55% were arterial thromboses, 146 cases (96.27%) were complicated with thromboses at diagnosis, and 36 cases (11.46%) showed newly thromboses or progression of previous thromboses among the 314 received full follow-up patients. Age (P＜0.001, HR:1.033, 95%CI:1.016-1.051), JAK2V617F mutation (P=0.037, HR:1.72, 95%CI: 1.033-2.862), hypertension (P＜0.001, HR:2.639, 95%CI:1.659-4.197) and hyperlipidemia (P＜0.001, HR:2.659, 95%CI:1.626-4.347) were the independent risk factors affecting thrombosis at diagnosis of the patients. During the follow-up, age (P=0.016, HR:1.032, 95%CI: 1.006-1.059) and previous thrombosis history (P=0.019, HR:2.194, 95%CI: 1.135-4.242) were the independent risk factors affecting the progression of thrombosis at different sites or on the basis of the previous thrombosis in the patients. CONCLUSION Patients with advanced age, JAK2V617F mutation or complicated with hypertension and hyperlipidemia shows a higher risk of thrombosis at diagnosis, while the patients with advanced age or previous thrombosis history shows a higher risk of progression of thrombosis during the follow-up.
Humans ; Myeloproliferative Disorders/genetics* ; Neoplasms ; Philadelphia Chromosome ; Risk Factors ; Thrombosis

Objective To investigate the correlation between the polymorphism of 4 coagulation-related genes, rs1799963 （coagulation factor V gene Leiden）, rs6025 （prothrombin gene G20210A）, rs1042579 （thrombomodulin protein gene c.1418C>T） and rs1801131 （methylenetetrahydroflate reductase gene） and lower extremity deep venous thrombosis （LEDVT）. Methods The 4 genotypes mentioned above of 150 LEDVT patients and 153 healthy controls were detected by the kompetitive allele specific polymerase chain reaction （KASP）, then related blood biochemical indicators were collected, binary Logistic regression was established to screen the independent risk factors of LEDVT, and the correlation between polymorphism of 4 coagulation-related genes and LEDVT and its indicators under different genetic modes after adjusting confounding factors were analyzed. Results Five variables, D-dimer, fibrinogen degradation product, homocysteine, sex and age might be the risk factors of LEDVT. These variables were put into 4 genetic inheritance models, and adjusted in binary Logistic regression. The results suggested that the mutations of rs1042579 were correlated with LEDVT under dominant inheritance mode. Conclusion The gene polymorphism of rs1799963, rs6025 and rs1801131 has no significant correlation with the formation of LEDVT. The gene polymorphism of rs1042579 plays a role under dominant inheritance mode, and might be an independent risk factor for formation of LEDVT.
Blood Coagulation/genetics* ; Humans ; Lower Extremity ; Polymorphism, Genetic ; Risk Factors ; Venous Thrombosis/genetics*

Factor VIII/genetics* ; Gene Duplication ; Humans ; Male ; Thrombosis/genetics*

Adult ; Aged ; Female ; Heparin, Low-Molecular-Weight ; Humans ; Janus Kinase 2 ; Male ; Mutation ; Sinus Thrombosis, Intracranial ; etiology ; Thrombocythemia, Essential ; complications ; genetics

BACKGROUNDRecently, calreticulin (CALR) gene mutations have been identified in patients with essential thrombocythemia (ET). A high-frequency of ET cases without Janus kinase 2 (JAK2) mutations contain CALR mutations and exhibit clinical characteristics different from those with mutant JAK2. Thus, we investigated the frequency and clinical features of Chinese patients of Han ethnicity with CALR mutations in ET.

METHODSWe recruited 310 Chinese patients of Han ethnicity with ET to analyze states of CALR, JAK2V617F, and MPLW515 mutations by polymerase chain reaction and direct sequencing. We analyzed the relationship between the mutations and clinical features.

RESULTSCALR, JAK2V617F, and MPLW515 mutations were detected in 30% (n = 92), 48% (n = 149), and 1% (n = 4) of patients with ET, respectively. The mutation types of CALR involved deletion and insertion of base pairs. Most of them were Type 1 (52-bp deletion) and Type 2 (5-bp insertion, TTGTC) mutations, leading to del367fs46 and ins385fs47, respectively. The three mutations were exclusive. Clinically, patients with mutated CALR had a lower hemoglobin level, lower white blood cell (WBC) count, and higher platelet count compared to those with mutated JAK2 (P < 0.05). Furthermore, a significant difference was found in WBCs between wild-type patients (triple negative for JAK2, MPL, and CALR mutations) and patients with JAK2 mutations. Patients with CALR mutations predominantly clustered into low or intermediate groups according to the International Prognostic Score of thrombosis for ET (P < 0.05).

CONCLUSIONSCALR mutations were frequent in Chinese patients with ET, especially in those without JAK2 or MPL mutations. Compared with JAK2 mutant ET, CALR mutant ET showed a different clinical manifestation and an unfavorable prognosis. Thus, CALR is a potentially valuable diagnostic marker and therapeutic target in ET.

Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; genetics ; Biomarkers ; analysis ; Calreticulin ; genetics ; Female ; Humans ; Janus Kinase 2 ; genetics ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Mutation ; Receptors, Thrombopoietin ; genetics ; Thrombocythemia, Essential ; genetics ; pathology ; Thrombosis ; genetics ; Young Adult

OBJECTIVETo explore the high risk factors of thrombosis in paroxysmal nocturnal hemoglobinuria (PNH). It has been reported that in Chinese patients with venous thrombosis, the mutation frequency in PROC c.574_576 del (rs199469469), PROC c.565C>T (rs146922325) and THBD c.-151G>T (rs1698852) was higher than that of normal controls, indicating its importance in thrombophilia pathogenesis.

METHODS142 patients with PNH diagnosed between 2009 and 2015 were enrolled in the study. Clinical data were analyzed and thrombophilia risk factors, such as the level of protein C, protein S, antithrombin III, APC resistance, blood fat, phospholipid antibody, were evaluated. Samples from patients and 100 normal controls were detected for the mutations of PROC c.574_576 del (rs199469469), PROC c.565C>T (rs146922325) and THBD c.-151G>T (rs1698852) by Sanger sequence.

RESULTSOf the 142 PNH patients, 21 (14.8%) patients had at least 1 episode of thrombotic event. Only 2 patients had arterial thrombosis and 19 patients had venous thrombosis. The median age of patients with thrombosis was 35 years old, similar to those without episode (40 years old, P=0.687). The ratios of males and females were 1.33 in thrombosis group and 1.57 in non-thrombosis group (P=0.728) , respectively. Patients with thrombosis had the same disease pattern compared with those without episode. Although there was no difference in the level of hemoglobin, WBC and PLT count, and LDH level between patients with thrombosis and those without episode, patients with thrombosis showed higher RBC, higher percentage of CD59(-) granulocytes and RBC, and Flaer(-) granulocytes compared with those without episode. The routine thrombophilia screening tests did not show any difference either between PNH patients and normal controls, or between patients with or without thrombosis. There were two mutations in rs199469469 and rs16984852 sites in patients with PNH, but the mutated patients did not have any thrombosis. Mutation rs146922325 was found in PNH patients. The mutation rate was similar between PNH patients and normal controls, thrombotic PNH and non-thrombotic PNH (P>0.05).

CONCLUSIONSCompared with non-thrombotic patients, PNH thrombotic patients have bigger PNH clone and higher RBC count. There are no differences among the routine thrombophilia factors and the three known venous eligible genes either between PNH patients and normal controls or between thrombotic and non-thrombotic PNH patients.

Adult ; Antithrombin III ; metabolism ; Case-Control Studies ; Clone Cells ; cytology ; Female ; Granulocytes ; cytology ; Hemoglobinuria, Paroxysmal ; genetics ; physiopathology ; Humans ; Leukocyte Count ; Male ; Protein C ; metabolism ; Protein S ; metabolism ; Risk Factors ; Thrombosis ; genetics ; physiopathology

BACKGROUND: Currently, the hypertension (HTN) patients undergo appropriate medical treatment, and traditional risk factors are highly controlled. Therefore, potential risk factors of atherosclerotic vascular diseases (AVD) and venous thromboembolisms (VTE) in HTN should be reconsidered. We investigated thrombophilic genetic mutations and existing biomarkers for AVD or VTE in HTN patients receiving treatment. METHODS: A total of 183 patients were enrolled: AVD with HTN (group A, n=45), VTE with HTN (group B, n=62), and HTN patients without any vascular diseases (group C, n=76). The lipid profile, homocysteine (Hcy) levels, D-dimers, fibrinogen, antithrombin, lupus anticoagulant, and anti-cardiolipin antibody (aCL) were evaluated. Prothrombin G20210A, Factor V G1691A, and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C were analyzed. RESULTS: All patients revealed wild type prothrombin G20210A and Factor V G1691A polymorphisms. The frequency of MTHFR polymorphisms was 677CT (n=84, 45.9%); 677TT (n=46, 25.1%); 1298AC (n=46, 25.1%); and 1298CC (n=2, 1.1%). The MTHFR 677TT genotype tended to increase the odds ratio (OR) to AVD events in HTN patients (OR 2.648, confidence interval 0.982-7.143, P=0.05). The group A demonstrated significantly higher Hcy levels (P=0.009), fibrinogen (P=0.004), and platelet counts (P=0.04) than group C. Group B had significantly higher levels of D-dimers (P=0.0001), platelet count (P=0.0002), and aCL (P=0.02) frequency than group C. CONCLUSIONS: The MTHFR 677TT genotype and Hcy level could be potential risk factors associated with development of AVD in HTN patients receiving treatment. D-dimer and aCL might be useful to estimate the occurrence of VTE in them.
Adult ; Aged ; Antihypertensive Agents/therapeutic use ; DNA/analysis ; Factor V/genetics ; Female ; Fibrin Fibrinogen Degradation Products/analysis ; Genotype ; Homocysteine/blood ; Humans ; Hypertension/*complications/drug therapy ; Lipids/blood ; Male ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics ; Middle Aged ; Odds Ratio ; Platelet Count ; Polymorphism, Single Nucleotide ; Prothrombin/genetics ; Real-Time Polymerase Chain Reaction ; Republic of Korea ; Risk Factors ; Vascular Diseases/*etiology/genetics ; Venous Thrombosis/*etiology/genetics