Hemostasis Research Articles

The purpose of this study is to determine the prognostic value of factor signs for the effectiveness of anticoagulant and antiplatelet therapy in patients with severe COVID-19. Materials and methods: The frequency of cerebrovascular complications in severe COVID-19, the background of comorbid conditions of the cardiovascular continuum, the levels of hemo stasis and inflammation markers were studied. Results: With a sum of prognostic indicators equal to 2.7, the probability of developing cere brovascular complications is less than 1 %. With a prognostic indicator equal to 34.41, the probability of developing cerebrovascular complications approaches 100 %. Conclusions: The proposed prognostic scale, which takes into account the pathogenetic features of the relationship between markers of inflammation and coagulation, should be used in the treatment of patients with severe COVID-19 to identify the cohort of patients at high risk of developing cerebrovascular complications by summing the prognostic indicators depending on the presence of comorbid conditions of the cardiovascular continuum and the levels of markers of inflammation and thrombosis.

CIB1 Regulates Hemostasis through Integrin Outside-in Signaling

Tonsillectomy has generally been regarded as an in-patient procedure. Presently though, due to rising costs and space constraints, it has increasingly became popular as a day case procedure world-wide. However, careful selection of patients is advised so as to avoid undue risks and possible resulting mortalities. To find out the suitability or otherwise of day case tonsillectomies in a resource poor country, taking note of possible complications arising from the surgeries and also pre-operative management modalities adopted to prevent these. Case notes of 52 Patients who underwent day case tonsillectomies and Adenotonsillectomies over a nine year period were reviewed. Indication for Surgery was recurrent tonsillitis for 11 (25.6) children and Adenotonsillar Hypertrophy for 32 (74.4%) children. The indication for surgery of all the adults was recurrent tonsillitis. Data extracted included age, sex, indication for surgery, procedure used for both Anesthesia and Surgery and complications arising from Surgery. 52 Patients met the criteria for day case surgeries. 43 (82.7) were Children and 9 (17.3%) were Adults. 49 patients (94.3) recovered well except 3 (5.7%) patients who had had complications and had to be admitted overnight afterwards. 1(1.9%) patient represented in the Hospital following earlier discharge for overnight admission. Day case Tonsillectomies/Adenotonsillectomies are relatively safe procedures especially when patients are carefully selected and pre-operative measures to encourage heamostasis instituted. Key words: Day case, costs, tonsillectomies, complications, haemostasis.

Sponsoring Organizations: American Society of Hematology, International Society on Thrombosis and Haemostasis, National Hemophilia Foundation, and

Innate Immune Cell-Derived Phospholipids and Hemostasis

Principles of Agnikarma and its Advances for Shonitsthapana (Hemostasis)

DILEMMA OF SYSTEMIC ANTICOAGULATION: A COVID-19 PATIENT WITH SPONTANEOUS CHEST WALL HEMATOMA

The sensitivity to heparin during cardiopulmonary bypass (CPB) is determined by patient-specific characteristics and is assessed by the whole blood activated clotting time (ACT). We aimed to examine reliability measures between two different ACT monitors using Bland-Altman analysis: bias should not exceed 50 ± 50 seconds for measurements performed during CPB or 10 ± 10 seconds before and after CPB. The ACT response should be linear in relation to the concentration of heparin in plasma. Twenty patients (n = 20) aged 20-80 years and admitted for coronary artery bypass surgery were enrolled to this clinical observational study. ACT values and antifactor Xa were sampled: 1) before induction of anesthesia, 2) after heparin bolus, 3) during CPB at the start of rewarming, 4) at weaning from CPB, and 5) after heparin reversal. The evaluation comprised the Hemostasis Management System Plus™ (HMS, Medtronic Inc., Minneapolis, MN) and i-STAT™ (Abbott, Point of Care Inc., Princeton, NJ). Bias for the HMS Plus™ vs. i-STAT™ was +105 ± 119 seconds for measurements during CPB and +2.8 ± 11.7 seconds before and after CPB. Associated limits of agreement for the observed bias were ±235 and ±23 seconds, respectively. Inter-device correlation of ACT values was .46 (p < .001) during CPB; otherwise .48 (p = .02). Both devices produced ACT values unrelated (<10%) to the measured heparin concentration. The use of multivariable regression analysis demonstrated an independent association between the ACT measurement and hematocrit, however, not with the plasma concentration of heparin. ACT monitors demonstrate unacceptable bias differences, combined with wide limits of agreement. The ACT response correlated with hematocrit, but not with the actual heparin concentration.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used to support patients with reversible cardiopulmonary insufficiency. Although it is a lifesaving technology, bleeding, inflammation, and thrombosis are well-described complications of ECMO. Adult porcine models of ECMO have been used to recapitulate the physiology and hemostatic consequences of ECMO cannulation in adults. However, these models lack the unique physiology and persistence of fetal forms of coagulation factors and fibrinogen as in human infants. We aimed to describe physiologic and coagulation parameters of piglets cannulated and supported with VA-ECMO. Four healthy piglets (5.7-6.4 kg) were cannulated via jugular vein and carotid artery by cutdown and supported for a maximum of 20 hours. Heparin was used with a goal activated clotting time of 180-220 seconds. Arterial blood gas (ABG) was performed hourly, and blood was transfused from an adult donor to maintain hematocrit (Hct) > 24%. Rotational thromboelastometry (ROTEM) was performed at seven time points. All animals achieved adequate flow with a patent circuit throughout the run (pre- and post-oxygenator pressure gradient <10 mmHg). There was slow but significant hemorrhage at cannulation, arterial line, and bladder catheter sites. All animals required the maximum blood transfusion volume available. All animals became anemic after exhaustion of blood for transfusion. ABG showed progressively declining Hct and adequate oxygenation. ROTEM demonstrated decreasing fibrin-only ROTEM (FIBTEM) clot firmness. Histology was overall unremarkable. Pediatric swine are an important model for the study of pediatric ECMO. We have demonstrated the feasibility of such a model while providing descriptions of physiologic, hematologic, and coagulation parameters throughout. Weak whole-blood clot firmness by ROTEM suggested defects in fibrinogen, and there was a clinical bleeding tendency in all animals studied. This model serves as an important means to study the complex derangements in hemostasis during ECMO.

Monsel’s solution has been in use since the end of the 19th century for its valuable property of creating hemostasis in minor disruptions of the epithelium. Its styptic effect was first described by Leon Monsel, a pharmacist in the French army, in a letter dated on October 13, 1852. Containing ferric subsulphate, it is used as a topical hemostatic agent in minor procedures such as biopsies in gynecology, proctology, dermatology, otorhinolaryngology and odontology. A 28-year-old nulliparous woman, with a known history of adenomyosis, had presented for sudden heavy intermenstrual vaginal bleeding. Examination revealed a bleeding Nabothian cyst. Monsel’s solution application helped stop the bleeding. She returned 3 days later with persistent heavy vaginal bleeding. Examination showed active oozing from the Nabothian cyst. A cervical smear and a human papillomavirus (HPV) swab were taken, and vaginal packing was inserted. The cervical smear result was reported as atypical cells, suspicious for malignancy. Colposcopy performed showed a grade 2 acetowhite lesion, suspicious for cervical intraepithelial neoplasia (CIN) III/microinvasive disease. However, punch biopsies of the cervix revealed only CIN I/koilocytosis. The patient was counselled and subsequently underwent a laser cone biopsy, which showed CIN I with clear margins. The discrepant results between the cervical smear and the cone biopsy prompted a review of the cervical smear and cervical histology; and a relook at the chronology of events. The cytological features observed in the initial cervical smear could be explained by the interference from the Monsel’s solution, which was applied just 3 days before the cervical smear. In cases where Monsel’s solution has been used for hemostasis, it is best to delay taking a cervical smear or a biopsy for at least 3 weeks as the histologic effect of Monsel’s solution may persist for up to that duration of time in tissues. J Med Cases. 2020;11(10):324-326 doi: https://doi.org/10.14740/jmc3556

Ureteropelvic junction obstruction (UPJO) is characterized by decreased flow of urine down the ureter and increased fluid pressure inside the kidney. Open pyeloplasty had been regarded as the standard management of UPJO for a long time. Laparoscopic pyeloplasty reports high success rates, for both retroperitoneal and transperitoneal approaches, which are comparable to those of open pyeloplasty. However, open and laparoscopic pyeloplasty have yielded disappointing failure rates of 2.5%-10%. The main causes for recurrent UPJO are severe peripelvic and periureteric fibrosis due to urinary extravasation, ureteral ischemia, and inadequate hemostasis. In addition, failing to diagnose lower pole crossing vessels before or during the primary procedure is also responsible for recurrent UPJO. In addition, poor preoperative split renal function, hydronephrosis, presence of renal stones, patient age, diabetes, prior endopyelotomy history, and retrograde pyelography history were considered as predictors of pyeloplasty failure. The failure is usually defined by persistent pain, persistent radiographic obstruction (infection or stones), continued decline in split renal function, or a combination of the above. And the failure of pye-loplasty often occurs in the first 2 years after the surgery. The available options for managing recurrent UPJO with a salvageable renal unit include endopyelotomy, re-do pyeloplasty, stent implantation, percutaneous nephrostomy, ureterocalicostomy, and nephrectomy. Re-do pyeloplasty has such merits as high successful rates and rare complications, compared with endopyelotomy or ureterocalicostomy. And some investigators think that re-do pyeloplasty should be regarded as the gold standard for secondary therapy if feasible. Open pyeloplasty can enlarge the operating field, facilitate the exposure of the ureteropelvic junction, reduce the difficulty of operation, and thus reduce the occurrence of complications. There are no significant differences among the success rates of re-do pyeloplasty under open approach, traditional laparoscopy and robot-assisted laparoscopy, according to previous reports. However, traditional laparoscopic and robot-assisted pyeloplasty give advantages of cosmetology, small trauma, less postoperative pain, speedy recovery and shorter hospitalization, fewer complications and lower recurrent rates. If the primary pyeloplasty is an open operation in retroperitoneal approach, the traditional laparoscopic and robotic operation with retroperitoneal approach should be considered for secondary repair. The cause of recurrent UPJO should be evaluated before surgery and identified intraoperatively to minimize the possibility of recurrence.

Sponsoring Organization: International Society on Thrombosis and Haemostasis (ISTH)Background and ObjectivesManagement of splanchnic vein thrombosis

Carotid blowout syndrome is an uncommon and fatal medical emergency in patients with head and neck cancer. Tumor progression, previous surgery, and radiotherapy on the head and the neck regions are some of the predisposing factors that affect its presentation. An early suspicion of a carotid blowout syndrome allows early safety measurements to prevent catastrophic events. A 71-year-old man with advanced base of tongue cancer was presented with a self- limiting oral bleeding 18 months after receiving chemoradiotherapy. Fiberoptic laryngoscopy and contrast-enhanced computed tomography revealed the presence of edema of the hypopharynx and thyroid cartilage fracture and necrosis. The patient developed acute oral hemorrhage. Surgical intervention was insufficient to achieve hemostasis. The carotid angiography revealed a common carotid artery rupture, and a covered stent was placed endovascularly. The covered stent placement was enough to stop the bleeding. However, the patient died from perioperative complications. Experience is necessary for the early detection and prevention of a carotid blowout syndrome.

В отсутствие достаточной базы доказательной медицины самым ценным становится мнение экспертов, опирающихся на свой опыт и опыт коллег. COVID-19-ассоциированная коагулопатия имеет характер тромбовоспаления. Назначение гепаринов — нефракционированного или, главным образом, низкомолекулярного (НМГ) призвано преодолеть его, поскольку гепарин обладает не только антикоагулянтным эффектом, но и оказывает непрямое и прямое противовоспалительное дейст вие. Поэтому назначение НМГ как минимум в профилактических дозах показано всем госпитализированным пациентам. Система гемостаза у пациентов с COVID-19, прежде всего у тяжелых, требует лабораторной оценки количества тромбоцитов, содержания Д-димера, протромбинового отношения или процентов протромбина по Квику и концентрации фибриногена. Анализ данных показал, что своеобразие коронавирусного гемостаза формирует гиперфибриногенемия, которая становится явным фактором гепаринорезистентности. Для преодоления последней назначение увеличенных (промежуточных или лечебных) доз НМГ выглядит перспективным решением. Достаточность назначения уместно определить либо по анти- Ха активности или (как экспресс-оценка) по тромбоэластрограмме. In the absence of a suffi cient base of evidence-based medicine, the most valuable becomes the expert’s opinion as a mirror of both personal and collegial experience. COVID-19-associated coagulopathy has a character of a thromboinfl ammation. The heparins — unfractionated or mainly low molecular weight heparins (LMWH) are intended to overcome it, since heparins have not only an anticoagulant effect but both an indirect and direct anti-infl ammatory effects as well. So that LMWH are indicated for all in-hospital patients. Patients with COVID-19, especially in severe cases, require laboratory testing of platelet count, D-dimer, prothrombin ratio or prothrombin percents by Quick and fi brinogen. Data analysis showed that a feature of coronavirus hemostasis is hyperfibrinogenemia that becomes an overt factor for heparin resistance. To overcome the latter, an adjusting doses of LMWH toward intermediate or therapeutic looks like a promising way. The suffi ciency of the adjusted LMWH dose is appropriate determining either with anti- Xa activity or thromboelastographically as express testing. Key words: hemostasis, COVID-19-associated coagulopathy, fibrinogen, low molecular weight heparins

The Effect of Sulphated Cellulose on Haemostasis

A 58-year-old male patient diagnosed with thromboangiitis obliterans (Fontaine stage IV) was recently treated with microendoscope discectomy system-assisted spinal cord stimulation electrode implantation and cured by department of vascular surgery combined with department of spinal surgery at Peking University People's Hospital. The patient suffered from cold injury to the right foot 14 years ago, which was cold, painful, numb, and then the toe was ulcerated and gangrene. Only the right foot small toe was left. The right foot skin was swollen from the toe to the proximal segment 1 year ago, accompanied by resting pain. Both pain and autologous bone marrow stem cell transplantation were ineffective. The above symptoms were aggravated three months ago, and the pain was severe. The visual analogue score was 10 points. A high amputation of the left lower extremity was performed 30 years ago due to trauma. Physical examination: the bilateral femoral artery was weak, and the right radial artery, posterior tibial artery, and dorsal artery were not touched. Buerger sign (+). Auxiliary examination: angiography of both lower extremities showed complete occlusion of the bilateral external iliac artery and its distal end. The percutaneous oxygen partial pressure was measured to be 30 mmHg on the right side of the iliac crest. The operation was performed under the local anesthesia. After X-ray positioning, the body projection of the lumbar vertebrae 1-2 lamina gap was marked. The skin had a 1.8 cm incision on the caudal side 2 cm from the mark. Then the dilators were used, and the working sleeve was tilted to the lumbar vertebrae 1-2 lamina gap. The microendoscope discectomy system was installed, the electrode was directly placed into the epidural space from the interlamina space under the microendoscope, the vascular surgeon adjusted the position of the electrode in the spinal canal under fluoroscopy, then connected the stimulator, adjusted the current until the patient had the lower limb fever, fixed electrode position, removed the microendoscope discectomy system after hemostasis under the microendoscope, used the guide needle to lead the electrode through the lumbar subcutaneous and then sutured the incision. After the operation, the electrode was connected to the temporary stimulator to stimulate for several minutes, the patient felt numbness in his lower limbs. In less than one hour, the skin temperature of the affected limb increased, and the painkiller could be stopped while sleeping. After 1 week, the skin temperature of the affected limb increased, and the percutaneous oxygen partial pressure of the foot and ankle was 36 mmHg, and the pain improved, and the score was reduced to 2 points. One month after surgery, the patient underwent permanent stimulator implantation. The pain disappeared after 3 months and half year of follow-up, and the score was reduced to 1 point. Microendoscope discectomy system-assisted spinal cord stimulation electrode implantation can complete the operation quickly, safely and effectively, and greatly reduce the number of intraoperative fluoroscopy and reduce the occurrence of complications.

The problem of sepsis and septic shock has recently become more and more actual. In obstetrics and gynaecology, the number of cases of sepsis has more than doubled over the past 10 years. The review examines the clinical forms of septic conditions, risk factors, pathogenesis of sepsis and septic shock, the main pathogens of septic conditions. Special attention is paid to neonatal sepsis. The relationship between septic shock and viral infections is considered in the context of the novel coronavirus infection caused by SARS-CoV-2 (COVID-19) pandemic. Hemostasis abnormalities have been demonstrated in patients with septic shock, including disseminated intravascular coagulation (DIC). The importance of determining the level of ADAMTS-13 to refine the forecast is discussed.

Objective To introduce and discuss the efficacy of a new technique to perform transperitoneal single-docking robot-assisted laparoscopic nephroureterectomy (RNU). Methods A total of 44 patients diagnosed with urothelial neoplasm of the renal pelvis or were investigated from January 2016 to November 2019. RNU was performed by a single surgeon. Among the 44 patients, 31 were male, and 13 were female. The median age was 63 (IQR: 58-71). The median body mass index (BMI) was 23.08 (IQR: 21.55-24.60) kg/m2. All operations were performed with general anesthesia. The patients were positioned 80 degrees flank with the diseased side up, and the head was tilted 10 degrees downwards. The camera port was placed one finger lateral to the umbilicus. For the right-sided tumors, robotic arm 1 was inserted through the trocar on the right pararectus line, 8 cm above the umbilicus, and robotic arm 2 was inserted through the trocar on the same line, 8 cm below the umbilicus. Assistant trocar 1 was placed where the anterior midline joins the perpendicular bisector of the camera port and robotic 2, and assistant trocar 2 was placed below the xiphoid process. For the left-sided tumors, all trocars were centrosymmetric to that of the right-sided tumors, except that assistant port 2 was placed 3 finger width above the pubic symphysis. The peritoneum was incised along the Toldt line, and the inferior vena cava was isolated (for left sided tumor, the abdominal aorta was isolated instead). The renal artery and vein were clipped with Hem-o-lok and ligated, and the kidney were isolated. The ureter was identified and isolated downwards across the common iliac artery and then clipped distal to the tumor site. The bladder cuff was resected and sutured under the laparoscopy. Results The median operation time was 145 (IQR: 130-175) min, with the median console time of 119 (IQR: 108.5-136.0) min, the anastomosis of bladder cuff of 12 min, and the median estimated blood loss of 50(20-100)ml. After the surgery, 6 Clavien-Dindo grade 2 complications occurred, including 2 chylous leakage, 1 hemostasis, 1 blood transfusion, 1 deep vein thrombus, and 1 acute coronary syndrome. The median length of stay (LOS) was 8 (IQR: 6.5-10.0) d. The median length of follow-up was 12 months. In total, 5 patients were dead, including 3 cancer-specific death. Four recurrence occurred and caused 3 death. The 2-year overall survival and progression-free survival were 68.2% and 77.9%, respectively. Conclusions The technique of RNU with simultaneous bladder cuff excision (BCE). Our technique improved the surgical outcome. The perioperative complication rate was low, and the short-term survival outcomes were satisfactory. Key words: Ureteral neoplasms; Upper tract urothelial carcinoma(UTUC); Nephroureterecto-my; Robotic surgery; Laparoscopic surgery

Objective To analyze the clinical efficacy of coronary artery bypass grafting(CABG)in patients of advanced age with left main coronary artery disease(LMCAD). Methods From 2005 to 2014, 101 elderly patients(≥80 years)with LMCAD underwent off-pump CABG in our hospital.Among them, 82 were male and 19 were female, with an average age of(81.4±1.7)years.Seventy-six cases(75.2%)had significant left main stenosis(≥70%)and twenty-five cases had left main stenosis less than 70%.The average left ventricular end diastolic diameter was(48.2±8.3)cm; left ventricular ejection fraction was more than 50% in 89 cases and 30% to 50% in 12 cases.Fourteen cases had mitral insufficiency and one had ventricular aneurysm.In addition, 56 patients had New York Heart Association functional classification Ⅰ to Ⅱ, and 45 patients had classification Ⅲ to Ⅳ.Ninety-nine patients had Canadian Vascular Society(CCS)classification of angina pectoris Ⅰto Ⅲ, two had classification Ⅳ and thirteen had acute myocardial infarction.Six patients were implanted with intra-aortic balloon counterpulsation before CABG. Results The average operation time was(3.9±0.8)h, the average number of bridging vessels were(3.0±1.0)roots, ICU monitoring time was(50.2±46.0)h, and ventilator assisted breathing time was(42.9±68.5)h.Six patients(5.9%)had secondary thoracotomy hemostasis, five(4.9%)had secondary tracheal intubation, and four(4.0%)had continuous dialysis.Intra-aortic balloon counterpulsation was implanted in 3cases(2.9%)during operation and in 11 cases(10.9%)after operation.Two cases(2.0%)had perioperative myocardial infarction and 8 cases(7.9%)died after operation during hospitalization.The median follow-up time was 6(1-11)years, and 17(16.8%)had all-cause mortality. Conclusions Although the two independent high-risk factors, old age and left main stenosis often coexist, off-pump CABG and perioperative management are still safe and effective treatments. Key words: Coronary disease; Coronary artery bypass, off-pump

Objective To investigate the protective effect of laparoscopic water separation and removal combined with suture hemostasis on ovarian reserve function after bilateral ovarian endometriotic cyst (OEC) stripping. Methods From January 2016 to January 2018, 60 patients with bilateral ovarian endometriosis cystectomy underwent laparoscopic surgery in the Department of Obstetrics and Gynecology, Jiading Hospital of traditional Chinese medicine.According to the random number table method, they were divided into study group (water separation and stripping combined suture hemostasis group) and the control group (direct stripping combined with electrocoagulation hemostasis group), 30 cases in each group.The changes of operation time, hemoglobin level before and after operation and the levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and anti Mullerian hormone (AMH) were compared between the two groups. Results There was no significant difference in operation time (47.52 ±10.11) min, hemoglobin decrease (0.55 ±0.26) g/L, hospital stay (6.1 ±0.3) d, control group (48.01 ±10.24) min, hemoglobin decrease (0.56 ±0.25) g/L and hospitalization time (6.2 ±0.4) d before and after operation (t=0.056, 0.964, 0.863, all P>0.05). The levels of FSH, E2, LH and AMH in the study group before operation were (6.15 ±2.31) U/L, (152.41 ±41.40) nmol/L, (5.44 ±1.52) U/L and (2.21 ±0.13) μg/L, respectively.One month after operation, they were(6.21±2.24) U/L, (150.63±40.33) nmol/L, (5.13±1.58) U/L, (2.18±0.16) μg/L, respectively.Three months after operation, they were (6.52±2.41) U/L, (149.57±42.37) nmol/L, (5.30±1.45) U/L, (2.17± 0.15) μg/L, respectively.Six months after operation, they were (6.53±2.44) U/L, (151.36±41.54) nmol/L, (4.98±1.61) U/L, (2.20±0.08) μg/L, respectively.The levels of FSH, E2, LH and AMH in the control group before operation were (6.14±2.21) U/L, (153.31±40.39) nmol/L, (5.51±1.46) U/L, (2.23±0.13) μg/L, respectively.One month after operation, they were (8.11±2.44) U/L, (131.43±41.23) nmol/L, (5.92±1.64) U/L, (1.58±0.14) μg/L, respectively.Three months after operation, they were (8.42±2.35) U/L, (135.67±40.38) nmol/L, (6.12±1.51) U/L, (1.54±0.16) μg/L, respectively.Six months after operation, they were (9.17±2.64) U/L, (133.66±40.44) nmol/L, (6.28±1.74) U/L, (1.51±0.13) μg/L, respectively.There was no significant difference in the levels of FSH, E2, LH and AMH between the two groups (all P>0.05). There was significant difference between the preoperative FSH level and the postoperative 1, 3, 6 months in the control group (all P<0.05); there was significant difference between the preoperative E2 level and the postoperative 1 month in the control group (P<0.05); there was statistical significance between the preoperative AMH level and the postoperative 1, 3 months in the control group (all P<0.05). The levels of FSH, LH, E2 and AMH in the study group were significantly higher than those in the control group (all P<0.05). Conclusion Laparoscopic hydrodissection combined with suture hemostasis does not increase the operation time and the amount of bleeding, and does not affect the ovarian reserve function after operation. Key words: Ovarian endometrioma; Hydrodissection; Suture hemostasis; Ovarian reserve function