Abstract OBJECTIVE: To observe the mechanism of action of how the application of low molecular heparin calcium improves the survival rate of severed finger replantation, and to provide a theoretical basis for better clinical application of low molecular heparin calcium. Methods:Through a clinical randomized controlled trial design, 30 patients with broken fingers were studied and 30 healthy adults were used as reference subjects. The changes of blood rheological indexes in 30 patients with finger amputation were observed at different time periods before and after surgery. Results:The blood rheological indexes were significantly increased from injury to 72 h after surgery in the patients with severed fingers, and there was a significant difference compared with the control group (P<0.01). Low-molecular heparin calcium can significantly reduce the blood viscosity of the patients with severed finger reimplantation, improve the blood unfavorable to the survival status of the severed finger, improve the survival rate of the severed finger, and reduce its necrosis rate and disability rate. Conclusion: Low-molecular heparin calcium, with little toxic side effects, is a good drug to prevent and treat the postoperative complications of finger replantation and provides a more ideal treatment method for successful replantation of severed fingers in clinical practice.
Key words: replantation of severed fingers; low molecular heparin calcium; blood rheology; clinical study
C.I.C.: Q-93-33 Document ID: A Article ID.
Lowmolecularweightheparincalciumonclinicalstudyofhemorheologicaleffectofsmallvascularinjuryafteroperation
MENGXin1,YUEQi1YUEWei-jie1LIWei1,△MENGQing-gang2,△
(1HarbinMedicalUniversity,HarbinCity,HeilongjiangProvince,150001,China;2ThefirsthospitalofHarbinCity,HarbinCity, HeilongjiangProvince,150001,)
ABSTRACTObjective:Tostudytheapplicationoflowmolecularheparincalciumcanimprovethesurvivalrateofreplantationofseveredfingermechanism ,toprovideabasisforclinicalrationalapplication.Methods:throughrandomizedcontrolledtrialdesign, 30casesofpatientswithreplantationofseveredfingersastheobjectofstudy,30healthyadultasreferenceobject.30 casesofreplantationofamputatedpatientsbeforeandafteroperationindifferentperiodsoftheindexesofbloodrheology.Results: Thepatientsinjuredfingertopostoperative72hhemorheologicalindexesweresignificantlyincreased, withsignificantdifferencecomparedwiththecontrolgroup(P<0.01). Lowmolecularweightheparincansignificantlyreducepatientwithreplantationofseveredfingerbloodviscosity, improvethebloodisnotconducivetothefingerstate,improvethesurvivalrateofreplantationofamputatedfinger,reducethenecrosisrate, disabilityrate.Conclusions:lowmolecularweightheparincalcium,lesstoxicsideeffect, amedicineforthepreventionandtreatmentofcomplicationsafterfingerreplantation, providesanidealtreatmentmethodfortheclinicalsuccessofreplantationofseveredfinger.
Keyword:Replantation;Lowmolecularheparin;Hemorheology;Clinicalresearch
ChineseLibraryClassification:Q-93-33Documentcode:AArticleID:
Preface
Currently, microsurgical techniques are widespread, and the survival rate for replantation of severed fingers is quite stable, with an estimated survival rate of 80C90 % [1-3]. Among them, avulsion injury is often a technical challenge and also causes many complications, vascular damage, causing endothelial fragmentation, tearing and other activation of the coagulation system, causing severe macroscopic and microscopic injuries [4-5]. The few cases that failed were mostly searched from different angles, without removing the already contused vessel wall and other aspects to find the cause, while often ignoring the changes in blood rheology after the patient’s injury [6]. We designed the experiment to observe the mechanism of action of how the application of low molecular heparin calcium improves the survival rate of severed finger replantation, and to provide a theoretical basis for better clinical application of low molecular heparin calcium.
1. Materials and methods
1.1 Study subjects
1.1.1 Case sources Between March 2010 and March 2011, patients with severed fingers were given in the Department of Hand Surgery of the Fourth Hospital of Harbin Medical University. 30 patients in the severed finger replantation group, with the same preoperative and postoperative conditions, and 30 patients in the control group were healthy physical examination patients, and there was no significant difference in the comparison of the basic conditions of the two groups. All subjects who participated in this experiment signed the informed consent form.
1.1.2 General information There were 30 patients with severed fingers, 17 males and 13 females, aged 14 to 50 years old, with an average age of 26.7-1.7 years. Among them, there were 16 cases of single finger severance, 9 cases of 2 finger severance, and 5 cases of 3 finger severance. Causes of injury: 15 cases of cutting injury, 15 cases of chainsaw injury. The plane of finger severance: 8 fingers at the end joint, 12 fingers at the distal interphalangeal joint, 5 fingers at the middle joint, and 5 fingers at the proximal interphalangeal joint. In the control group, there were 30 cases, including 14 males and 16 females. The age was 18 to 54 years old, with an average of 28.1 s 1.9 years. There was no statistically significant comparison between the two groups in terms of gender and age (P>0.05).
1.2 Study methods
1.2.1. Experimental design This experiment selected two groups of patients who met the inclusion criteria for control observation. Blood was collected in the broken finger reimplantation group 1h before surgery, 0h, 1h, 6h, 24h, 48h, 72h, 7d and 14d after surgery (refer to Sun’s blood collection method). In the control group, blood was collected in the morning on an empty stomach, and 3 ml of venous blood was taken into heparin anticoagulation bottles for each collection, and the indexes were tested within 2 h. The whole blood high and low cut viscosity values, plasma viscosity, erythrocyte specific volume, platelet adhesion rate, fibrinogen and other indexes were examined in both groups to study the pattern of blood rheology in patients with finger amputation to guide clinical prediction of vascular crisis.
1.2.2. Surgical methods [7-8] Patients were actively prepared preoperatively after admission, generally with brachial plexus block anesthesia, and care was taken to avoid accidental removal of blood vessels and finger nerves trapped in subcutaneous tissues during debridement, with emphasis on microscopic debridement. For severed fingers with neat trauma and short severance time, the bone stent is routinely fixed, the tendon is sutured, and the artery is anastomosed, and the blood vessels are locally flushed intermittently with 10-100u/ml isotonic saline of low-molecular heparin calcium injection during the anastomosis. Incisions allow extensive contact for reimplantation of severed fingers, and lateral incisions have been proposed, but they are difficult to approach without compressing the vessels. Nerves and vessels were identified and marked after meticulous debridement of tourniquet-controlled inactivated tissue. Bone shortening (between 0.5 and 1 cm) allows soft tissue repair and ensures tension-free anastomosis of the vascular nerve. Bone fixation and alignment must be ensured to allow early postoperative movement and tendon adhesions. There are several methods of bone fixation (kerf pins for internal fixation, intraosseous wires, intramedullary wires, tetrahedral wires, pins, plates, and screws) and multiple combinations thereof. Periosteal and soft tissue repair should be done with care to prevent tendon adhesions and secondary probing. From a dorsal approach, the extensor tendon can be repaired. Under venous repair, unless there is a determination of prolonged or difficult venous ischemia, at least two veins and vein graft repair should generally be necessary. Early arterial repair is advocated by some authors in order to re-establish early reperfusion of the tissue, exclude tissue ischemia from metabolites, and promote venous return.
1.2.3 Treatment [9] Experimental drug Low molecular heparin calcium injection:0.4ml:4100AXaIU/branch, GlaxoSmithKline (Tianjin) Co. In the experimental group, low-molecular heparin calcium was given once daily by subcutaneous abdominal injection 2 hours before surgery and on the day after surgery until 14 days. Postoperatively, patients were strictly bedridden and should be arranged to rest quietly in a quiet, comfortable and airy ward after surgery. Maintain humidity and temperature, perioperative anticoagulation, and application of low molecular heparin calcium and aspirin for replantation of severed fingers, with dosages chosen according to the different surgeons and units; there are no prospective data to support the standard treatment regimen for any of these drugs. Antibiotics should be continued for approximately 1 week.
1.2.4 Testing indicators and treatment ①Blood collection time:Blood will be collected at the same time as above and the indicators will be tested within 2h. ②Blood rheology indexes:The indexes are performed with the instrument to detect whole blood high and low cut viscosity values, plasma viscosity, erythrocyte specific volume, platelet adhesion rate, and fibrinogen.
1.3 Statistical methods
SPSS11.5 statistical software was used for the analysis. One-way ANOVA and t-test were used for the comparison of measurement data, and the results were expressed as mean±standard deviation (x±s), and the difference was considered statistically significant at P<0.01. The analysis of clinicopathological data and other count data was performed by χ2 test, and the difference was considered statistically significant at P<0.05.
2, Results
2.1 Treatment results
Of the 49 fingers in 30 cases, 46 fingers were viable and 3 fingers failed (2 completely severed fingers and 1 incompletely severed finger), and the probe was caused by vascular stubborn spasm, and no thromboembolism was caused by the failure of this group, and the survival rate reached 93.87%; 45 cases had good functional recovery after surgery, and 1 case had limited activity function and recovered well by functional exercise.
2.2 Blood rheology test results of patients with severed fingers
Compared with the control group, the blood rheological indexes such as whole blood viscosity, plasma viscosity, erythrocyte specific volume, platelet adhesion rate and fibrinogen were significantly higher at 72h after surgery (P<0.01, P<0.05). This indicates that the blood viscosity of the patients increased significantly after the injury and the coagulation effect was enhanced. The blood rheological indexes basically returned to normal after 72 h after the completion of finger replantation surgery, and there was no statistical significance when compared with the control group (P>0.05), indicating that the blood viscosity of the postoperative patients gradually became normal and the blood flow was smooth, see Table 1 and Table 2.
Table1resultsofblood rheology in patients with severed fingers from injury to 72h postoperatively (x±s)
Table1resultsofseveredfingerinjuryto72hofHemorheologyinthepatientswithpostoperative(x±s)
surveillanceproject
Digitalgroup(30cases)
Thecontrolgroup(30cases)
Wholebloodviscosity(15s-1)
8.57s-0.13
8.09s-0.04*
Wholebloodlowshearviscosity(150s-1)
7.76 s0.12
6.43S0.18*
Plateletadhesionrate(%)
41.99S5.12
31.76sh2.21*
fibrinogen(g/L)
4.98-1.45
3.08S1.08*
plasmaviscosity
1.78S0.34
1.12S0.07**
erythrocrit(%)
47.21S4.09
31.41sh3.54*
Note:*P<0.05;**P<0.01 for the two groups.
Note:twogroup*P<0.05;**P<0.01
Table272haftertheblood rheological test results of patients with broken fingers after 272h(x±s)
Table272hafterthebloodrheologyinpatientswithreplantationresults(x±s)
surveillanceproject
Digitalgroup(30cases)
Thecontrolgroup(30cases)
Wholebloodviscosity(15s-1)
8.09s-0.21
7.99s-0.09
Wholebloodlowshearviscosity(150s-1)
6.89S0.26
6.86s0.31
Plateletadhesionrate(%)
35.43S5.13
32.21S4.32
fibrinogen(g/L)
3.87S1.05
3.65S1.13
plasmaviscosity
1.48S0.18
1.56S0.11
erythrocrit(%)
41.09S4.09
31.12S3.87
Note:P>0.05 for the two groups.
Note:twogroupP>0.05.
3.Discussion
3.1 Characteristics of blood rheological changes after reimplantation injury
In this experiment, it was found that the blood rheology indexes were uniformly increased in patients from injury to 72h postoperatively, which was statistically significant when compared with the control group. Probing the cause revealed that the endothelium is damaged and the endogenous coagulation system is activated rapidly, while the coagulation cascade reaction is triggered by the release of tissue factors from tissue injury or vascular injury, tissue factors form complexes in the presence of calcium, factor VIIa and coagulation factors X and IX its active forms (factor Xa and IXA), prothrombinase complexes, and then assembled in phospholipid membranes and cleaved thrombinogen (factor II ) on factor IIa (thrombin). Prothrombin is one of the most effective activators of primary (platelet-mediated) and secondary (coagulation factor-mediated) hemostasis [9-10]. In addition, calcium oligomeric heparin exerts its antithrombotic effect after finger amputation reimplantation by direct, selective, and reversible binding to the active site of thrombin. This leads to thrombin-catalyzed or inhibited induced reactions, including fibrin formation, activation of coagulation factors V, VIII, XIII, protein C, and platelet aggregation. Microthrombi are formed [11-12]. Most of the postoperative blood rheological indicators in our cases were abnormal, suggesting the possibility of vascular crisis. After postoperative symptomatic treatment, such as the input of anticoagulant drugs and replenishment of blood volume, the blood gradually returned to a normal state. Therefore, it is recommended to apply anticoagulation and other treatments in the perioperative period.
3.2 Significance of rheological index testing in the replantation of severed fingers
At present, microsurgical techniques are popular, and the survival rate of severed finger replantation is quite stable, with an estimated survival rate of 80C90 %. However, functional scoring of severed fingers is difficult to achieve after transplantation. One of the technical challenges is often the circumferential avulsion injury. Vascular injury, causing endothelial fragmentation, tearing and other activation of the coagulation system, causes severe macroscopic and microscopic damage [13]. The few cases that fail are mostly sought from different angles, without looking for causes such as resection of the already contused vessel wall, while often ignoring the changes in the patient’s post-injury blood rheology [13-14]. Changes in blood rheological parameters are relatively small in healthy individuals, but in some cases, when there are no clinical symptoms yet, abnormalities in certain blood rheological indicators may occur, and the use of blood rheology methods may provide predictive information for certain diseases. Therefore, this study investigates the blood rheology pattern of patients with amputated fingers through the detection of blood rheology indexes in different time periods, which can provide theoretical basis for the prevention and treatment of vascular crisis in clinical practice.
3.3 Inadequate perfusion is also an important factor that induces abnormal blood rheology and other indexes
Most of the patients have insufficient blood volume and hematoconcentration before emergency surgery, which cause the indexes such as erythrocyte specific volume and whole blood viscosity to increase significantly, thus predisposing to the formation of thrombus. Therefore, it is recommended that early anticoagulation therapy should be accompanied by massive rehydration, but as much as possible in elderly patients [15]. Postoperatively, fluid drips should be maintained, especially at night, to maintain effective blood pressure and allow vascular filling and rapid blood flow, thus preventing thrombosis, which is the main cause of early failure on replantation after replantation of severed fingers. Most statistics find the frequency of this complication to be 0.8% to 20%. Its pathogenesis is complex. Reducing the amount of circulating blood flow before replantation of a severed finger can cause thrombosis, whether performed with different kinds of vascular anastomoses. The effect of changes in the reimplantation of severed fingers on the human microcirculation leads to thrombosis of veins and is expressed by the following sequence: reperfusion cell death – edema – increased resistance to blood flow and other factors. The application of such a method can improve the success rate of replantation [16]. In conclusion, this experimental study confirms that most of the indicators in patients with severed fingers have abnormal blood injury up to postoperative period, and the above indicators can be used as biochemical indicators to predict the occurrence of vascular crisis. Therefore, the early use of anticoagulant drugs and the administration of anticoagulant therapy before or during the resurfacing of severed fingers are beneficial to improve the survival rate of severed fingers.
The main strategy for prevention and treatment of thrombosis after replantation of severed fingers remains the primary task. A wide range of direct thrombin inhibitors such as low molecular heparin, sulforaphane, and warfarin are usually reserved for those patients who require treatment. New oral anticoagulants in the postoperative period have now become a clinical development and are expected to be used with their use and more favorable efficacy moderated instead of drugs with more complications, bleeding is the main adverse event of concern, but calcium low molecular heparin is able to reduce the occurrence of such adverse events [17,18]. On the other hand exerting its antithrombotic effect is through direct, selective, and reversible binding to the active site of thrombin. This leads to thrombin catalysis or inhibition of induced reactions, including fibrin formation, on coagulation factors V, VIII, protein C activation, and platelet aggregation [19-21]. In our patients, low molecular heparin calcium was routinely given once daily subcutaneously in the abdomen 2 hours preoperatively and on the same day postoperatively until 14 days, without monitoring coagulation, and no patients had a bleeding tendency. Most of the fingers were viable, and those that were not were promptly explored for vascular recalcitrant spasm caused by the failure of this group without thromboembolism, with a survival rate of 93.87%. Therefore, we believe that using this drug intraoperatively and postoperatively is safe, can reduce complications, reduce the economic burden for patients, and provide a more ideal treatment method for successful clinical replantation of severed fingers.