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Case report

Acute thrombocytopenic crisis following burns complicated by staphylococcal septicaemia

Alexander George a, Rameshwar L. Bang a,b,*, Abdul-Reda Lari a, Raj K. Gang a
a

Al -Babtain Centre for Plastic, Reconstructi6e Surgery & Burns, Ibn -Sina Hospital, Kuwait b Department of Surgery, Faculty of Medicine, PO Box 24923, Safat 13110, Kuwait Accepted 22 March 227

Abstract The pathophysiological changes in a burn patient can at times manifest as severe complications, the management of which can be extremely challenging to the burn surgeon. A case report of an adult male with burns (18% total body surface area) who developed an acute unexpected thrombocytopenia crisis (2 109 l 1) on day 3 followed by disseminated intravascular coagulation is presented. The various etiological factors and possible mechanisms leading to thrombocytopenia in burns are discussed. Minor burns may present acute major complications in the presence of other thrombocytopenic factors like trauma and sepsis and thrombocytopenia by it self can be a good indicator of sub-clinical infection. 2001 Elsevier Science Ltd and ISBI. All rights reserved.
Keywords: Thrombocytopenia; Staphylococcus aureus ; Burns; Disseminated intravascular coagulation; Trauma

1. Case report A 27-year-old male was referred to our burn centre with a history of being assaulted with st cuffs followed by his clothes being set on re. Cutaneous examination revealed 18% total body surface area (TBSA) burns of the neck, chest and both upper limbs; most of which were second degree supercial dermal except for 2% which was deep dermal. Further examination revealed some contusions on the face and both lower limbs along with a 0.5 cm subcutaneous deep wound on the thigh. There was no evidence of pulmonary inhalation injury and systemic examination did not show any injury to major organs. The patient was resuscitated using the Parkland formula, the burn areas were dressed with povidone iodine and Pethidine (meperidine) was administered as analgesia. Radiological survey and ultrasonography ruled out the presence of any
* Corresponding author. Tel.: + 965-531-9475; fax: + 965-5319597. E -mail address: rameshwar@hsc.kuniv.edu.kw (R.L. Bang).

fractures and evidence of internal trauma. His laboratory investigations were: HCT 0.460, HB 15.8 g dl 1, WBC 16.6 109 l 1, platelet 355 109 l 1, RBC 5.45 1012 l 1, serum albumin 44 g l 1, serum protein 81 g l 1, blood urea 4.1 mmol l 1, serum creatinine 44 mol l 1, blood sugar 5.2 mmol l 1, serum sodium 138 mmol l 1 and serum potassium 4.1 mmol l 1. Until the second post burn day the patient was stable but febrile (38.2C) for which he received oral paracetamol (acetaminophen). On the third post burn day while the patient continued to show low grade fever (38C), the intravenous (i.v.) uids were discontinued as his uid intake and output were adequate. All the laboratory parameters were within normal limits except for a severe thrombocytopenia (2 109 l 1). In view of such a low platelet count the blood sample was again examined and found to conrm the previous reading. On the fourth post burn day the patient developed bluish discoloration and swelling at the site of trauma over the face and both lower limbs. Examination of the burn wound showed early signs of infection with multiple petechial haemorrhages and breakdown of eschar.

0305-4179/01/$20.00 2001 Elsevier Science Ltd and ISBI. All rights reserved. PII: S 0 3 0 5 - 4 1 7 9 ( 0 0 ) 0 0 0 6 5 - 6

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Wound swabs and a set of two blood samples were taken to isolate the causative organisms. Tazocin (piperacillin and tazobactam) and Amikin (amikacin) were started empirically and six units of platelets were transfused. Prothrombin time (PT), activated partial thromboplastin time (APTT), brinogen and brin degradation products (FDP) were within normal limits but the platelet count was low (31 109 l 1). On the fth post burn day pustules were found over the burn areas and the wound swab culture revealed the presence of Staphylococcus aureus. Tazocin was discontinued and Vancomycin (500 mg i.v. six hourly) was started as per sensitivity reports and also due to the possibility of a subclinical Methicillin resistant Staphylococcus aureus (MRSA) infection. The patient received fresh frozen plasma (FFP) and platelet transfusions. Although PT and APTT were normal again, brinogen levels and brin degradation products (FDP) were elevated and the patient was thought to be in disseminated intravascular coagulation (DIC). On the sixth post burn day, the patient developed high fever (39.5C) and bleeding from the burn wound. The platelet count fell to 1 109 l 1 and brinogen and FDP were elevated. Other investigations were within acceptable limits. On the seventh post burn day, Rifampicin 600 mg day 1 was added in consultation with the microbiologist as there was no signicant response to Vancomycin and Amikin. On the eighth post burn day, blood transfusion was given as the haemoglobin was low (9.8 g dl 1). The blood culture grew S. aureus and the
Table 1 Clinical data during the burn perioda PBD 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 19 22 25 28 PLT 355 304 2 31 8 1 18 27 17 36 191 72 222 361 511 627 725 529 391 331 HB 15.8 15.1 18.5 15.9 13.2 12.6 10.8 9.8 10.7 10.5 10.2 10.4 10.1 10.5 10.9 11.7 11 10.8 11.6 11.4 WBC 16.6 14.2 13 12.2 11.6 12.1 7.9 14 12.9 12.1 13.7 12.4 13.7 15.1 11 9.5 8.6 9.7 6.2 6.2 TEMP/C 37 38.2 38 37.5 38.4 39.5 39 39.3 37 37 37 37 37 37 37 37 37 37 37 37

patient continued to be febrile (39.3C). On the ninth post burn day, the patient became afebrile but the platelet count remained low (17 109 l 1) and FFP and platelet concentrate were administered. From the tenth post burn day the platelet began to rise (36 109 l 1) reaching normal levels on day 11 and all other laboratory investigations were within normal limits.While the patient was afebrile, the burn wounds began showings signs of healing and Amikin and RMP were discontinued. On the seventeenth post burn day, most of the areas had healed except for some deep patches on the chest (2%) which subsequently were excised and covered by skin graft. The platelet count rose to its highest (724 109 l 1) on the eighteenth post burn day, before its gradual declinc. On the 22nd post burn day Vancomycin was discontinued and the patient remained afebrile. The patient was discharged when all the burn areas as well as the skin grafted areas had healed after 28 days of hospital stay. Table 1 and Fig. 1 show the clinical data during the burn period.

2. Discussion Thrombocytopenia has been observed in animal experiments following both burns and trauma. In burned rats, an initial thrombocytopenia associated with an increased rate of platelet disappearance and reduced platelet survival is followed by thrombocytosis before a return to normal values [1]. Thermal injury in humans

WSCS NEG NEG STAPH A NEG NOR NEG

FIB/FDP

BDS

Antibiotics NA NA NA TAZAMI VANAMI VANAMI VANAMIRMP VANAMIRMP VANAMIRMP VANAMIRMP VANAMIRMP VANAMIRMP VANAMIRMP VAN VAN VAN VAN NA NA NA

RAISED RAISED RAISED STAPH A NOR

NEG NEG

NEG

NOR

NEG

a PBD post burn day, PLT platelet count, HB haemoglobin, WBC white blood corpuscles, TEMP/C temperature in degree centigrade, FIB/FDP brinogen/brin degradation products, WSCS wound swab culture sensitivity, BCS blood culture sensitivity, NEG negative, NOR normal, NA no antibiotic, STAPH A S. aureus, TAZ tazocin, AMI amikin, VAN vancomycin, RMP rifampicin.

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A. George et al. / Burns 27 (2001) 8488

Fig. 1. Chart showing the variations in platelet count during the entire burn period.

leads to thrombocytopenia, pseudothrombocytosis, secondary thrombocytosis, increased platelet adhesiveness and decreased platelet survival [2,3]. Although the large uid volumes in the early resuscitative phase cause a dilutional fall in platelets, thermal destruction and haemostatic mechanisms in the burn areas also consume large number of platelets. Burn tissues are known to release thromboplastin that causes microthrombi to form at distant sites such as the lungs and kidneys. The reticuloendothelial system of the body plays a vital role in removal of these microthrombi thereby further contributing to the thrombocytopenia [4 6]. Several colony stimulating factors, viz. macrophage colony-stimulating factor (M-CSF), interleukin-3 (IL-3) and interleukin-6 (IL-6), induce the production of megakaryocytes by the bone marrow and derangement in their levels may contribute to thrombocytosis that occurs in the later phase of burns [7]. The patient had minor burns (18%) which was unlikely to have caused a dilutional thrombocytopenia during resuscitation. The area of the burns being mainly supercial dermal with a small deep dermal patch (2%) could not have caused a major thermal destruction of platelets. Heideman et al. studied thrombocytopenia following soft tissue trauma and observed aggregation of thrombocytes in blood and trappings in the lung subsequent to hindleg injuries in dogs [8]. Although severe thrombocytopenia is described in massively traumatised patients [9], in our case the patient had minor trauma that certainly did not account for the problem he confronted.

Bacterial sepsis is often accompanied by thrombocytopenia but the mechanisms responsible have not been clearly identied [10]. The possible factors for thrombocytopenia in septicemia could be: direct bone marrow suppression, increased platelet destruction, presence of endotoxins, production of platelet autoantibodies, hypersplenism, haemophagocytosis and DIC leading to consumption of platelets [1117]. It is believed that M-CSF and cytokines may be causing the activation of macrophages and monocytes leading to haemophagocytosis [18]. The patient had a severe thrombocytopenic crisis on the third post burn day before the clinical manifestation of burn wound infection (day 4) and before the isolation of any organism (day 5). While both the burn and the trauma were minor and by themselves unlikely to have caused the thrombocytopenic crisis, the superimposition of septicemia may have precipitated the acute thrombocytopenic crisis. The delicate balance of the clotting system is disturbed in severely burned patients and they show a state of transient DIC that is related to development of organ failure and ultimate outcome [19]. Burn patients have been shown to have a reduction in concentration of heparin, brinogen, antithrombin III, brinolysis and plasminogen activators, with simultaneous increase in the concentration of antiplasmins (alpha-2macroglobulin and alpha-1-antitrypsin) [1921]. Trauma also activates the clotting system and complement, a hypercoagulable state follows that could result in DIC [2224]. Uncompensated DIC is often a manifestation of major burns and trauma and it is quite

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likely that the infection must have activated an uncompensated DIC in the patient as both his burn and trauma were minor. A variety of drugs used in the management of the burn patient can induce thrombocytopenia: penicillin, piperacillin, vancomycin, rifampicin, acetaminophen, cimetidine, ranitidine, diazepam, chlorpheniramine, morphine and tetanus toxoid [25]. Silver sulphadiazine by itself has also been mentioned as a likely cause of thrombocytopenia [26]. The patient received paracetamol and pethidine prior to the development of thrombocytopenia and the local wound was dressed with betadine, all of which were unlikely to have caused the thrombocytopenia. Although paracetamol is known to cause thrombocytopenia, we do not think it played a role in this case as the patient had taken paracetamol in the past without any known reactions and in addition he also received it during the course of his surgery without any reduction in his platelet count. While postoperative thrombocytopenia had been reported in nonburn patients, Takashima reported the unexpected death after a session of skin grafting of two burn patients who developed severe thrombocytopenia postoperatively [27,28]. In our case, the patients who developed thrombocytopenia did so on the third post burn day in the absence of any surgical intervention and postoperatively, platelets rose their highest level (724 109 l 1). The management of thrombocytopenia remains complex as the causes are many and the exact mechanisms remain unknown. Platelet transfusions should be considered when the count is below 50 109 l 1 and with counts below 10 109 l 1 random platelet transfusions should be given [29]. Wound infection was apparent clinically only a day after the platelet count had fallen to 2 109 l 1 and proved bacteriologically 2 days later. Antibiotics were therefore started empirically and then specically based on sensitivity reports. MRSA infection continues to be an endemic problem in our unit and hence vancomycin was started in the absence of any positive evidence. Rifampicin was added, as there seemed to be no response to vancomycin, following which the patient responded positively [30]. It has been shown that endogenous IL-11 gene expression is upregulated during acute thrombocytopenia and bacterial sepsis in neonatal rats, though this increase does not prevent thrombocytopenia [31]. Exogenous IL-II administration enhances platelet recovery and improves survival and reduces the severity of thrombocytopenia in neonatal rats [31]. Brean et al. [32] injected small subcutaneous doses of heparin into patients with burns from the moment of admission and found signicantly less platelet deciency than in patients who did not receive heparin. In experimental studies the administration of prostaglandin 12 analog OP 41483 (Venopirin) helped suppress platelet reduction [33]. The management of DIC must address the underlying disease (trig-

ger), interrupt the activated haemostatic system and replace the consumed coagulating constituents, viz. platelet concentrate, FFP, clotting factor concentrate, cryoprecipitate and erythrocytes to raise the oxygen carrying capacity [14]. While interruption of haemostasis in DIC with heparin may be attempted with the risk of bleeding,the administration of antithrombin III has been shown to reduce the severity of DIC in septic patients [14]. Antithrombin levels reduce early after burns due to increased capillary leak and haemodilution but routing administration of antithrombin III in early uncomplicated burns is not warranted [34]. The patient received FFP and platelet transfusions only as replacements. Initially, the platelet counts rose transiently after the administration of platelet infusions but later it continued to rise steadily, a pattern probably related to the control of infection. The patient did not receive IL-II, heparin, prostaglandin analogue, OP 41483 or antithrombin III. Their use in burn patients will need further studies. Patients with extensive burns can develop pancytopenia, with the anaemia resulting from hypoproduction of differentiated erythroid progenitors or intramyeloid destruction of early erythroid cells and the neutropenia occurring due to an accelerated neutrophil consumption [35]. Though the patient developed a severe acute thrombocytopenic crisis, the RBC and WBC remained near normal. Both the burn and trauma were minor, but the combination of burn, trauma and sepsis proved a toxic cocktail precipitating an acute thrombocytopenic crisis. Minor burns need to be specially addressed in the presence of other complicating factors if fatalities are to be avoided.

Acknowledgements We are extremely thankful to Mrs. Jessy George for her secretarial help.

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