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Biomedical subjects

J Groh

Publications and source records attributed to J Groh.

At least 19 recordsLinked to original sources

[Continuous peridural analgesia vs patient - controlled intravenous analgesia for pain therapy after thoracotomy].

OBJECTIVES: Continuous epidural analgesia (EA) and patient-controlled intravenous analgesia (PCA) are widely used for postoperative pain control. Studies indicate that both analgesic regimens provide good analgesia after major surgery. However, because of the following reasons it is still unclear whether one of the two modes of application is superior. First, there are conflicting data regarding the differences in pain relief and drug use between epidural and intravenous administration of opioids. Second, in many studies epidural analgesia is performed by a combination of local anaesthetics and opioids. Third, reduced morbidity was observed only in some of the studies, in which epidural analgesia provided better pain relief than systemic opioid supply. Despite these conflicting results, EA with local anaesthetics and fentanyl as well as PCA with piritramid, a highly potent mu-agonist, are routinely used in Germany. The purpose of this study was to compare these two treatments for analgesic efficacy, pulmonary function, incidence of side effects and complications in patients undergoing thoracotomy. METHODS: In this prospective randomized trial 50 patients were included. For postoperative pain control 25 patients (EA group) received thoracic epidural infusion of local anaesthetics (bupivacaine 0.125% or ropivacaine 0,2%) and fentanyl 4,5 microg/ml with a flow rate of 4-10 ml/h. 25 patients received intravenous PCA with piritramid (bolus 2, 5 mg, lock out 15 minutes, maximum of 25 mg/4 h, no background infusion). RESULTS: Analgesia at rest and while coughing, as evaluated by visual analogue scale, was significantly better in the EA group. EA also resulted in superior values of pulmonary function tests, general condition and a lower incidence of sedation and nausea. In contrast, patients with EA reported distinctly more pruritus than patients with PCA. Duration of hospital stay was shorter in the EA group, but this difference did not reach statistical significance. There was one atelectasis in the EA group. No major complications related to EA or PCA were observed. CONCLUSION: In this study EA with local anaesthetics and fentanyl provided superior postoperative pain control and a lower incidence of sedation and nausea compared to intravenous PCA with piritramid, but there was no superiority as to pulmonary complications and duration of hospital stay.

Analgesia, Patient-Controlled↗

[Unilateral phrenic nerve paralysis after vertical infraclavicular plexus block] .

We present a case of a rapid onset reversible phrenic nerve block following vertical infraclavicular blockade of the brachial plexus. Five minutes after injection of local anaesthetics the SpO2 fell to 80%. Oxygen supplementation was required during the perioperative period to maintain normoxemia. The postoperative X-ray showed an elevated diaphragm of the ipsilateral side. After five hours oxygen supply could be terminated, an X-ray control the next day showed normal bilateral diaphragm position.

Aged↗

Lung procurement by low-potassium dextran and the effect on preservation injury. Munich Lung Transplant Group.

BACKGROUND: This clinical study was performed to evaluate the effect of low-potassium dextran (LPD) solution on organ function in human lung transplantation. METHODS: A total of 80 patients were included in this study. Donor lungs were flushed with Euro-Collins (EC) solution in 48 cases or LPD (Perfadex) in 32 cases. Subsequently, single- (EC: n = 31; LPD: n = 15) or double-lung transplantations (EC: n = 17; LPD: n = 17) were performed. The evaluation parameters of transplant function were the reperfusion injury score (grade I to V); the alveolar/arterial oxygen ratio; the duration of respirator therapy; and the length of intensive care treatment and survival. RESULTS: Incidence and severity of reperfusion injury score were more severe in the EC group (31 of 48: grade I: n = 13; II: n = 8; III: n = 5; IV: n = 2; V: n = 3; LPD group: 17 of 32 patients; grade I: n = 12; II: n = 1; III: n = 3; IV: n = 0 grade V: n = 0), leading to death in three patients. In the LPD group, despite of the use of cardiopulmonary bypass, alveolar/arterial oxygen ratio values were significantly (P = 0.009) better during the early postoperative phase. Thirty-day mortality was 12% in the EC group and 6% in the LPD group. The one-year survival rate was 79% after the use of LPD (vs. EC: 62%). CONCLUSIONS: Graft preservation using LPD leads to better immediate and intermediate graft function after pulmonary transplantation and also results in better long-term survival.

Adult↗

Cardiopulmonary exercise testing before and after lung and heart-lung transplantation.

Heart-lung (HLT) and lung transplantation (LT) have been shown to be effective procedures for patients with end-stage cardiopulmonary disorders. As yet, few data exist on the exercise performance of patients before and after thoracic transplantation except with regard to 6-min walk tests. In this article we report cardiopulmonary exercise test results of lung and heart-lung transplant recipients in comparison with their pretransplant values. We studied 103 consecutive recipients of single-lung (n = 46), bilateral lung (n = 32), and heart-lung (n = 25) transplants. Cardiopulmonary exercise testing with a cycle ergometer was performed before and shortly after surgery. Before transplantation, all patients showed severe exercise intolerance and markedly impaired parameters reflecting cardiopulmonary function (e.g., work capacity: 20 +/- 11% predicted; oxygen uptake: 34 +/- 12% predicted; oxygen pulse: 50 +/- 18% predicted; functional dead space ventilation: 57 +/- 10% of minute ventilation; alveolar-arterial oxygen difference during exercise: 79 +/- 15 mm Hg). At 55 +/- 9 d after transplantation, transplant recipients reached maximum oxygen uptakes in the range of 22 to 71% of predicted values; the peak oxygen uptake was increased after transplantation (13.1 +/- 3.4 ml/min/kg versus 10.4 +/- 3.8 ml/min/kg; p < 0.001). Work capacity, oxygen pulse, tidal volume, and peak minute ventilation did not differ in patients following single- or double-lung tranplantation or HLT. Ventilatory factors did not appear to limit exercise capacity in any group. Despite the persistent limitations in aerobic capacity and work rate seen in many of the recipients, cardiopulmonary performance is reasonably well restored shortly after LT and HLT.

Adult↗

Expression of adhesion molecules on circulating polymorphonuclear leukocytes during orthotopic liver transplantation.

After ischemia-reperfusion, polymorphonuclear leukocytes (PMNLs) become activated by inflammatory mediators, adhere to the vascular endothelium via the interaction of specific adhesion molecules, and cause tissue injury by the release of cytotoxic oxygen radicals and enzymes. Results obtained in animal experiments suggest a key role for PMNLs in ischemia-reperfusion injury of transplanted livers; therefore, we studied the expression of adhesion molecules on circulating PMNLs (beta2-integrins [CD18] and L-selectin [CD62L]) in 20 patients undergoing orthotopic liver transplantation (study group). To determine the effects of surgical trauma to the liver in the absence of ischemia and reperfusion, the expression of PMNL adhesion molecules was measured in 10 patients scheduled for elective partial liver resection without hepatic vascular exclusion (control group). Patients were classified as responders or nonresponders based on changes in the expression of adhesion molecules elicited by reperfusion. In the control group, all patients remained nonresponders, showing that surgical trauma of the liver alone does not cause activation of circulating PMNLs. In contrast, 8 of 20 patients in the study group were classified as responders. In responders, postoperative serum liver enzyme activities were significantly higher than in nonresponders, indicating that activation of PMNL was associated with damage to hepatocellular integrity. Because expression of adhesion molecules was already changed during surgery, monitoring of the expression of beta2-integrins and L-selectin on circulating PMNLs during orthotopic liver transplantation might be useful in prediction of early graft dysfunction.

Adolescent↗

Microhemodynamics and leukocyte sequestration after pulmonary ischemia and reperfusion in rabbits.

OBJECTIVE: Investigation of leukocyte sequestration in alveolar capillaries and of microhemodynamic changes after pulmonary ischemia/reperfusion injury. METHODS: The kinetics of leukocyte passage and the hemodynamics in pulmonary microcirculation were investigated in 16 rabbits by intravital microscopy. Mean red blood cell velocity and the number of sticking leukocytes were measured in pulmonary arterioles, venules, and capillaries after 1 hour of tourniquet ischemia and 10 minutes and 1 hour after reperfusion. RESULTS: The decrease of red blood cell velocity after reperfusion was associated with a largely increased heterogeneity of blood flow. Immediately after the onset of blood flow, sequestered leukocytes were found in all microvascular segments. An increased number of leukocytes was present in arterioles, venules, and alveolar capillaries 10 minutes and 1 hour after reperfusion. Concomitantly, width of alveolar septa was increased while arterial oxygen tension was reduced, indicating the development of interstitial pulmonary edema. CONCLUSION: Leukocytes are sequestered after pulmonary ischemia and reperfusion not only in alveolar capillaries but also in arterioles and venules, and they may contribute to the development of reperfusion edema.

Animals↗

Perioperative management of patients undergoing lung transplantation.

This review focuses on recent developments in the perioperative management of patients undergoing lung transplantation. Relevant current literature and the experience of the Munich Lung Transplant Group were taken into consideration. Recent advances include the use of inhalational nitric oxide for the treatment of early graft dysfunction and the use of aerosolized cyclosporine for the treatment of recurrent and steroid-resistant acute rejection. Opportunistic infections remain a major source of morbidity and mortality in lung transplant recipients.

Journal Article↗

Contribution of selectins to leucocyte sequestration in pulmonary microvessels by intravital microscopy in rabbits.

1. Sequestration of leucocytes in the lung is the net result of leucocyte rolling and sticking in pulmonary arterioles and venules and their retention in alveolar capillaries. 2. In order to investigate whether adhesion molecules of the selectin family contribute to these phenomena the effects of fucoidin (an inhibitor of L- and P-selectin) on microhaemodynamics and leucocyte kinetic were studied in pulmonary arterioles, capillaries and venules by means of intravital fluorescence microscopy in a rabbit model. 3. Fucoidin reduced leucocyte rolling in pulmonary arterioles and venules by 75 and 83%, respectively, without affecting leucocyte sticking. In alveolar capillaries, fucoidin reduced leucocyte retention and accelerated leucocyte passage, thus reducing the alveolar transit time of leucocytes by 62%. 4. It is concluded that rolling of leucocytes in pulmonary microvessels is mediated by selectins, whereas sticking relies on selectin-independent mechanisms. 5. Leucocyte retention in alveolar capillaries is not due solely to mechanical hindrance of leucocyte passage through narrow vessel segments, as previously hypothesized, but also depends on interaction of leucocytes with the capillary endothelium.

Animals↗

[The effects of aprotinin. Blood loss and coagulation parameters in orthotopic liver transplantation: A clinical-experimental, prospective and randomized double-blind study].

The effect of aprotinin (2,000,000 IU as a bolus +500,000 JU/h until the end of the operation) on transfusion requirements and coagulation parameters in orthotopic liver transplantation (study group: n = 9; placebo group: n = 9) was investigated in a randomised, double-blind study. Coagulation parameters were monitored intraoperatively using a mobile laboratory. In contrast to the published results, no effect on transfusion requirements could be demonstrated. However, aprotinin showed a positive effect on some coagulation parameters in the reperfusion phase. The mechanism appeared to be inhibition of the contact activation of the intrinsic system with less thrombin generation in the study group.

Aprotinin↗

[Discharge following ambulatory anesthesia].

Beyond strict selection of suitable patients the adequate choice of the best moment for discharge home is essential for safety and efficacy of outpatient surgery. Restitution of cardiovascular stability and psychomotoric function is completed at the end of observation in the recovery unit. Further prerequisites of home discharge are absence of postoperative nausea and vomitus as well as sufficient pain control by non-opioids and physical measures. The definition of fixed observation periods is unreasonable, technical examinations and psychomotoric tests are of minor importance. Home readiness has to be evaluated by a physician before discharge. Standardized scores or checklists may be of some help. The modalities of patient care after discharge are checked prior to surgery. During late postoperative recovery, continuous care of a responsible adult is required for at least 24 hours. During this time period certain restrictions must be respected, e.g. from driving and business contracts. Even after this time some residual effects of anesthesia may still be present.

Adult↗

[The anesthetist in perioperative care].

Due to the recent development in operative medicine medical and organizational demands on perioperative patient care have changed significantly. Corresponding to the responsibility of the operative colleagues for therapy of the primary disease, anesthesiologists have to account for monitoring and treatment of vital functions throughout the perioperative period, starting from preoperative evaluation until postoperative care. The postanesthesia recovery unit has a key role in perioperative management. Beyond post-operative monitoring and stabilization of vital parameters it is increasingly used as a buffer and switch operating station, where patients are prepared and allocated to a normal ward, an observation or intensive care unit for subsequent postoperative care. The recovery unit has developed to a "multitasking" care center, which should be operational 24 h a day with an anesthesiologist present during working hours. The terminology should be changed in the future in order to better characterize the new task spectrum, e.g. in perioperative anaesthetic care unit (PACU) for medical and medicolegal reasons patient security must have absolute priority above economic aspects. Effective postoperative pain control using epidural or patient-controlled intravenous analgesia may increase patient comfort and reduce postoperative complications caused by sympathoadrenergic activation. Both method can be safely used on normal wards provided that close cooperation and training of ward personnel is guaranteed as well as continuous supervision by a specialized acute pain service.

Anesthesia↗

[Neurologic complications following total endoprothesis implantation of the hip under peridural catheter anesthesia].

This case report describes paralysis of the plantar flexors and extensors after a total hip replacement in a 33-year-old woman performed under epidural anaesthesia (PDA). Six years previously, the patient had undergone a bone marrow transplantation for chronic myeloid leukaemia. She had developed a deep vein thrombosis, a pulmonary embolus, and a severe graft-versus-host reaction of the skin, leading to markedly reduced mouth opening. The hip operation was performed using PDA following antithrombotic prophylaxis with low-molecular-weight heparin. Blood could initially be aspirated after advancing the PDA catheter, and a second puncture of the epidural space 1 segment higher enabled correct placement of the catheter. The patient received 500 ml Dextran 60 perioperatively and the operation was completed without any further problems. The PDA catheter was removed 2 h after the operation following the return of movement of both thighs. Fourteen hours after the completion of surgery it was noticed that the dressing over the epidural puncture site was bloodstained, the patient was incontinent, and complete loss of movement of the operated leg was present. An epidural haematoma was the suspected cause, but could not be definitely confirmed by a CT scan. Nevertheless, a laminectomy was undertaken to evacuate the suspected haematoma. As expected, tracheal intubation was only possible bronchoscopically. Intraoperatively, some low-grade epidural oozing at the level of the initial puncture site was observed, and a hemilaminectomy of 5 was performed. For the first time postoperatively, the bleeding time was measured and was markedly prolonged to 20 min (as described by Mielke, normal value up to 8 min). A coagulopathy was suggested, with the differential diagnosis of impaired platelet function. The paralysis of the plantar flexors and extensors and some sensory loss were still present 6 months after the operation. It remains uncertain whether the PDA in a patient receiving low-molecular-weight heparin resulting in a the suspected epidural haematoma was the cause of the neurological sequelae and in agreement with the consultant neurologist, we believe that a direct traumatic lesion of the L5/S1 segment or damage to the sciatic nerve are also likely causes of the symptoms. Undoubtedly, the lack of adequate postoperative neurological monitoring and the intraoperative administration of dextran despite the known epidural vascular lesion deserve criticism. This case report demonstrates the often complex development of neurological complications after nerve blocks, where a definite cause can frequently not be determined.

Adult↗

[Thromboembolism prevention with low dose heparin and spinal anesthesia--a risky combination?].

UNLABELLED: Spinal or intracranial haematoma is a rare but severe complication of spinal/epidural anaesthesia with an incidence of less than 1:100,000. Coagulation defects, traumatic puncture, and anticoagulant drugs are assumed to be risk factors for the development of this kind of haematoma. Whether the risk of bleeding after spinal/epidural anaesthesia is increased by the administration of low-dose heparin (unfractionated or fractionated) for thromboprophylaxis is currently under discussion. METHODS AND RESULTS: A randomised, prospective trial answering this question is not feasible because of the rarity of the complication. As an alternative, we identified all case reports described in the literature to date and analysed them for possible risk factors. In conjunction with spinal/epidural anaesthesia, we found 4 cases of spinal and 2 cases of intracranial haematoma following treatment with unfractionated heparin and 6 cases of spinal haematoma following treatment with different low-molecular-weight (LMW) heparins. In none of these cases could thromboprophylaxis with heparin be identified as the only risk factor for bleeding: in 11 of the 12 cases a difficult or traumatic puncture was described. Eleven patients showed three or more possible risk factors, e.g., coagulation defects, concomitant therapy with other anticoagulant drugs, or anatomic abnormalities. CONCLUSION: We suggest that the development of spinal or intracranial haematoma after spinal/epidural anaesthesia is a multifactorial event. An influence of low-dose heparin prophylaxis as a cofactor cannot wholly be excluded because of the difficulty of studying the problem in a prospective way. The few case reports have to be seen in the context of millions of patients who have received either unfractionated or LMW heparin and lumbar or thoracic regional anaesthesia without any complication. We conclude that low-dose heparin prophylaxis (fractionated or unfractionated) is not a definite contraindication to spinal/epidural anaesthesia. High-risk (ASA III/IV) patients in particular benefit from effective postoperative analgesia achieved by local anaesthetics in combination with effective heparin thromboprophylaxis. Nevertheless, the absolute contraindications for regional anaesthesia must be respected and an individual risk/benefit analysis should be performed for every patient. An adequate time interval between application of heparin and regional anaesthesia or removal of a spinal/epidural catheter, atraumatic puncture technique, and careful neurologic monitoring during the post-operative period can minimise the risk of complications.

Anesthesia, Spinal↗

Results of liver transplantation for gastroenteropancreatic tumor metastases.

During the early 1980s liver transplantation (LTx) was expected to be a promising therapeutic option for patients with primary or secondary tumors confined to the liver. Because of disappointing results owing to death from early recurrence, LTx is currently restricted to well selected patients with small primary tumors and, in the case of liver metastases, to those with metastases of gastroenteropancreatic (GEP) tumor origin only. In our series of 300 liver transplantations four patients with GEP tumor metastases underwent LTx. The primary tumors were one neuroendocrine kidney tumor, one glucagonoma of the pancreas, and two cases of carcinoids of the pancreas. Because of local metastatic lymph node involvement upper gastrointestinal exenteration followed by LTx was performed in two patients. No patient survived beyond 33 months after LTx. Three patients died from tumor recurrence. In one patient who died from fungal sepsis autopsy revealed spine metastases that had been missed before LTx. Our dismal results do not compare well with promising data published previously by others for this particular patient group. Under the pressure of an increasing donor organ shortage, patients with GEP tumor metastases should be selected carefully for LTx.

Adult↗

Perioperative mucosal pH and splanchnic endotoxin concentration in orthotopic liver transplantation.

Although impairment of splanchnic perfusion may induce mucosal hypoxia and endotoxaemia during orthotopic liver transplantation (OLT), little is known about the changes in mucosal oxygenation during and after the procedure. To study the effects of liver surgery itself on mucosal pH (pHi) and the response of pHi to acute changes in portal flow, we measured gastric pHi during six liver resections using tonometry: in two patients, after clamping of the hepatoduodenal ligament, pHi decreased within 30 min and recovered promptly after reperfusion. We then investigated gastric and sigmoid pHi (pHig, pHis) during the perioperative phase in 18 OLT. Median pHi values were low before surgery (pHig 7.28 (first/third quartiles 7.22/7.34); pHis 7.27 (7.12/7.36)). Although global oxygen delivery and haemodynamic variables remained constant and veno-venous bypass (VVB) was used to maintain portal flow, pHi declined during the anhepatic phase (pHig 7.19 (7.13/7.23), P < 0.01; pHis 7.13 (7.06/7.24), P < 0.05). After reperfusion of the graft, pHi recovered and did not differ from baseline values by the end of OLT. After operation pHig increased further, reaching the highest values 30 h after ICU admission (7.34 (7.26/7.38)). In the intraoperative period, no significant endotoxaemia was observed either in portal or systemic blood. The maximum reduction in pHi was related neither to the duration of VVB and OLT nor to the number of red cell units transfused. pHi after reperfusion did not correlate with graft viability or dysfunction of the lung or kidney. We conclude that pHi indicates mucosal ischaemia during OLT which is not necessarily associated with endotoxaemia, and intraoperative pHi monitoring does not appear to be a valuable predictor of postoperative graft failure and organ dysfunction.

Adult↗

[The effect of mechanical ventilation, thoracotomy, and one-lung respiration on intrapulmonary perfusion distribution. An animal experimental study].

The physiological pattern of regional pulmonary blood flow is mainly determined by the relationship of pulmonary arterial, venous, and alveolar pressures. Changes in alveolar pressure and pulmonary geometry may therefore be expected to influence regional perfusion, which is a key determinant of pulmonary gas exchange. Unilateral thoracotomy is usually performed with the patient in the lateral decubitus position. The present study examined the influence of mechanical factors on regional pulmonary blood flow distribution in rabbits in the lateral decubitus position during normoxia and unilateral hypoxia. METHODS. Anaesthetised white New Zealand rabbits (n = 8) weighing 2200-3900 g (mean = 2860 g) received central venous injections of radioactive microspheres while in the left lateral decubitus position during spontaneous breathing (SB) and during mechanical ventilation (two-lung ventilation, 2LV), under closed (2LVC) and open chest (2LVT) conditions, as well as during unilateral hypoxia of the nondependent lung induced by nitrogen inflation (1LVN) or atelectasis (1LVA). The method used for one-lung ventilation (1LV) has been previously described in detail. Arterial, central venous, and pulmonary arterial pressures were recorded continuously. Lungs were excised, dried in the inflated state, and cut into 16 sagittal slices, which were further divided into lobar components, the lower lobes into center and periphery. The radioactivity of each specimen was measured in a gamma-counter; perfusion of the individual tissue specimens was quantified using the software program MIC III. The Friedman test followed by paired comparisons according to Conover was used for statistical analysis of differences between the experimental phases. Perfusion of central and peripheral parts of isogravitational slices was compared by use of the Wilcoxon matched pairs test. Values are given as means +/- SE; the level of significance was P < 0.05 unless otherwise indicated. RESULTS AND DISCUSSION. Haemodynamic parameters did not differ significantly between the experimental phases (Table 1). Compared to 2LV, a significant increase in venous admixture (P < 0.05) and a corresponding decrease in PaO2 (P < 0.01) were observed during 1LV. This effect was significantly more pronounced during 1LVA as compared to 1LVN (P < 0.01). Since inspiratory pressure was kept constant throughout the experiments, moderate respiratory acidosis developed during both phases of 1LV. Regional perfusion (Qr) of the nondependent lung was slightly reduced during 2LVC compared to SB and 2LVT. One-lung ventilation induced a significant decrease in perfusion of the hypoxic lung (P < 0.001 1LVN, 1LVA vs. SB,2LVC,2LVT). In accordance with the data obtained from blood gas analysis and oximetry, this effect was more pronounced during N2 insufflation than during atelectasis (P < 0.01 1LVN vs. 1LVA). Among the factors that may account for this effect, PaCO2 did not differ significantly between both phases of 1LV. During N2 insufflation PO2 at the hypoxia-sensitive site is lower than during atelectasis, where it equals mixed-versus PO2 (PvO2). The difference in local PO2 is unlikely, however, to have caused the changes in regional perfusion between 1LVN and 1LVA, since PvO2 was as low as 40 mmHg during 1LVA and the pulmonary vascular response to hypoxia has been found to reach its maximum in this PO2 range [2, 11]. Enhanced redistribution of regional perfusion during 1LVN as compared to 1LVA is therefore most likely attributed to differences in alveolar pressure and pulmonary geometry. Apart from a radial perfusion gradient in the right lower lobe during 2LVC and 2LVT, no isogravitational Qr gradients were observed. CONCLUSION. We conclude that controlled mechanical ventilation in the lateral decubitus position causes only minor changes in vertical blood flow distribution.

Animals↗

Quality control of platelet concentrates by the Thrombostat 4000.

Quality control of platelet concentrates (PC) is an important prerequisite for good transfusion praxis. However, direct measurement of platelet function is complex, since available methods (e.g. aggregometry, serotonin release) are time consuming and require special equipment. Therefore a test system is needed, which is easy to handle, fast, and achieves reliable results. The present paper compares the results of conventional platelet function tests with those of a modified in-vitro bleeding test (IVBT) (Thrombostat 4000) in liquid-stored and cryopreserved PCs. A high correlation between aggregometry, serotonin release, GMP 140 expression upon stimulation, and IVBT was demonstrated. Therefore IVBT seems to be a good alternative to the conventional platelet function tests for quality control of PCs. In addition, a good correlation between the results of IVBT of patients' blood after PC transfusion and IVBT of patients blood before transfusion supplemented with platelets of the respective PC could be found. Therefore IVBT seems to be able to predict PC transfusion success. However, since these data were obtained in a small sample undergoing bone marrow transplantation, further studies are needed to verify this hypothesis.

Bleeding Time↗