gms | German Medical Science

GMS German Plastic, Reconstructive and Aesthetic Surgery – Burn and Hand Surgery

Deutsche Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen (DGPRÄC)
Deutsche Gesellschaft für Verbrennungsmedizin (DGV)

ISSN 2193-7052

Management of disseminated bleeding in a patient with multiple malignomas using rotation thromboleastometry

Beherrschung von diffusen Blutungen bei einer Patienten mit multiplen Malignomen mit Hilfe der Rotationsthrombelastometrie

Case Report

  • corresponding author Jonas Kolbenschlag - BG Universitätsklinikum Bergmannsheil Bochum, Klinik für Plastische Chirurgie und Schwerbrandverletzte, Handchirurgiezentrum, operatives Referenzzentrum für Gliedmaßentumoren, Bochum, Germany; BG-Unfallklinik Ludwigshafen, Klinik für Hand-, Plastische und Rekonstruktive Chirurgie, Schwerbrandverletztenzentrum, Ludwigshafen, Germany
  • Gerhard Wittenberg - BG-Unfallklinik Ludwigshafen, Abteilung für Anästhesiologie und Intensivmedizin, Ludwigshafen, Germany
  • Marcus Lehnhardt - BG Universitätsklinikum Bergmannsheil Bochum, Klinik für Plastische Chirurgie und Schwerbrandverletzte, Handchirurgiezentrum, operatives Referenzzentrum für Gliedmaßentumoren, Bochum, Germany; BG-Unfallklinik Ludwigshafen, Klinik für Hand-, Plastische und Rekonstruktive Chirurgie, Schwerbrandverletztenzentrum, Ludwigshafen, Germany
  • Ole Goertz - BG Universitätsklinikum Bergmannsheil Bochum, Klinik für Plastische Chirurgie und Schwerbrandverletzte, Handchirurgiezentrum, operatives Referenzzentrum für Gliedmaßentumoren, Bochum, Germany; BG-Unfallklinik Ludwigshafen, Klinik für Hand-, Plastische und Rekonstruktive Chirurgie, Schwerbrandverletztenzentrum, Ludwigshafen, Germany

GMS Ger Plast Reconstr Aesthet Surg 2014;4:Doc05

doi: 10.3205/gpras000024, urn:nbn:de:0183-gpras0000244

Published: April 7, 2014

© 2014 Kolbenschlag et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Abstract

We report on a case of Klippel-Trenaunay syndrome with a histologically diagnosed dedifferentiated angiosarcoma. During operative tumor debulking, a disseminated bleeding developed which required a massive transfusion of red blood cell concentrates and therapeutic plasma. While plasmatic coagulation was within normal range, thromboelastometry showed a distinct hyperfibrinolysis. The bleeding was controlled by prolonged cauterisation and the substitution of tranexam acid as well as fresh frozen plasma. As a result of this treatment, hyperfibrinolysis showed complete restitution within a few hours. Histologically, a malignant peripheral nerve sheat tumor, a dedifferentiated angiosarcoma, a spindle cell sarcoma and an osteosarcoma were diagnosed within the tissue samples.

Keywords: hyperfibrinolysis, coagulation, Klippel-Trenaunay syndrome, sarcoma, haemorrhage

Zusammenfassung

Wir berichten über eine Patientin mit einem Klippel-Trenaunay-Syndrom. Nach mehreren auswärtigen Voroperationen zeigte sich zuletzt ein dedifferenziertes Angiosarkom. Im Rahmen der Tumorresektion kam es zu einer disseminierten Blutung die eine Massentransfusion von Erythrozytenkonzentraten und therapeutischem Plasma erforderlich machte. Bei normwertiger plasmatischer Gerinnung zeigte sich in der Rotationsthrombelastometrie eine ausgeprägte Fibrinolyse. Die Blutung konnte unter Gabe von Frischplasma und Tranexamsäure in Verbindung mit subtiler, langwieriger Kauterisierung beherrscht werden. Die Rotationsthrombelastometrie zeigte drei Stunden postoperativ bereits eine Restitutio ad integrum. Die Hyperfibrinolyse war nicht mehr nachweisbar. Histopathologisch wurden ein maligner peripherer Nervenscheidentumor, ein dedifferenziertes Angiosarkom, spindelzellige Sarkomanteile und eine osteosarkomatöse Dedifferenzierung diagnostiziert.


Medical history and diagnostic findings

A 49-year-old female patient reported a swelling of the lower right extremity, most prominent on the lower leg due to a Klippel-Trenaunay syndrome (KTS). Anamnestically, this situation was present since childhood and she had undergone several surgical interventions for reduction of tumor mass, mostly to improve her ability to wear shoes. Regarding further comorbidities, she reported a right-sided nephrectomy in 2010 due to recurrent pyelonephritic infections.

In 2010, the tumor at the right calf rapidly increased in size along with a newly found tumor of the thigh.

A MRI was performed, showing a diffuse lymph- and hemangiomatous infiltration of the entire soft tissue of the lower extremity with arterio-venous malformations and multiple lymphoceles. These had been punctured and sclerotized multiple times, which led to a strong bleeding from the ulcerated tumor during one such intervention, necessitating an emergency surgical intervention to achieve hemostasis.

Due to the resulting anaemia, a total of seven blood preservations had to be transfused. Plasmatic coagulation parameters were normal, however.

One week after, a surgical biopsy was performed alio loco to clarify the dignity of the lesion. Intraoperatively, the patient developed cardiac arrest. A pulmonary embolism was suspected and resuscitation as well as lysis was performed. This led to a full recovery of the patient without cardiac or neurological impairment. The biopsy samples showed wide-stretched tumor formations of a regressively transformed sarcoma. Therefore, due to the known KTS, a dedifferentiated angiosarcoma was suspected. During a pathology reference service however, a vascular tumor could not be seen. However, aspects of a spindle-cell sarcoma were observed.

For further diagnostics and therapy, the patient was referred to our hospital.


Course of treatment

On admission, we found a 50x20x20 cm large, ulcerated tumor on the dorsal right calf.

Imaging

To allow for an assessment of the dimension of the tumor and staging, we performed a MRI of the lower right extremity and the pelvis with contrast agents as well as a CT-scan of the thorax and a ultrasound examination of the abdominal organs. The findings on the calf confirmed the results of the previous MRI, showing an extensive, irregular perfused tumor. Nearly all of the muscle tissue as well as the fibula showed significant signal alterations, hinting at a possible infiltration by the tumor (Figure 1 [Fig. 1]). On the dorsal thigh, further wide-stretched tumor formations were found, also infiltrating the surrounding tissue (Figure 2 [Fig. 2]). In addition, the gluteal region showed a nodular accumulation of the contrast agent, suggesting further spreading of the tumor. Also, a suspect lymph node was seen in the right inguinal region.

While the ultrasound examination did not reveal any evidence for further filiae, the CT-scan brought up a suspicious pulmonary nodule in the right lower lobe of the lung.

Surgical intervention

The extensive findings were discussed with the patient and a radical resection with amputation of the lower right extremity was advised. After a lengthy consultation with the patient, she however refused the amputation. Therefore, only a surgical reduction of the tumor mass was performed (Figure 3 [Fig. 3], Figure 4 [Fig. 4]). The resected specimen measured 37x20x11 cm and weighted 3 kilograms. Due to a medical history of hypermenorrhoea as well as thrombophilia, extensive coagulation screenings were performed preoperatively. While INR, PTT as well as the amount of thrombocytes were within normal ranges, factor VIIIc was found to be slightly elevated at 207% (physiological range 70–200%) and the activity of Protein S was slightly reduced to 56% (physiological range 58–114%). Due to the known KTS as well as a malignancy and the coagulation findings, a thrombophilia was suspected, further backed up by the pulmonary embolism the patient sustained earlier.

However, a massive disseminated bleeding developed intraoperatively, necessitating extensive surgical hemostasis as well as the transfusion of a total of ten packs of blood and four packs of frozen plasma.

To assess the underlying disorder of the bleeding, a rotational thromboelastometry (RTE) was performed, showing a massive hyperfibrolysis (Figure 5 [Fig. 5]). By the administration of two grams of tranexam acid, the hyperfibrolysis could be reversed, as proven by another RTE three hours later (Figure 6 [Fig. 6]).

The histo-pathological findings revealed a malignant peripheral nerve sheath tumor (MPNST) with aspects of an osteosarcoma and were confirmed by a pathology reference service specialized in sarcomas.

Two weeks after the afore mentioned operation, an incisional biopsy of the tumor on the dorsal thigh was performed without any complications. It also revealed an MPNST upon hist-pathological examination.

Further course

The case was presented in our weekly interdisciplinary tumor board for a synopsis of the findings and the determination of the further course of treatment.

Due to the R2-situation on the right lower leg as well as the gluteal infiltration, a hemipelvectomy was considered as a potentially curative intervention. An indication for radiotherapy was not seen due to the massive extent of the malignancy. After a lengthy discussion of the findings with the patient, she deliberately decided not to have any further diagnostic or therapeutic interventions at all. She only allowed for local coverage of the soft tissue defect of the lower leg and a split-skin graft to the tumor. She was discharged thereafter and reported no further progress upon a follow-up appointment six weeks later in our outpatient clinic. Further care was administered in the patient’s neighbourhood, due to her explicit wish.


Discussion

The malignant peripheral nerve sheath tumor (MPNST) is a rare tumor entity. About the half of which arise from an underlying neurofibromatosis [1]. KTS on the other hand has been described in conjunction with several malignancies, including Hodgkin’s lymphoma, rhabdomyo- and angiosarcoma [2], [3], [4], [5].

However, there is only report of the coincidence of an MPNST, other sarcoma components and KTS in literature. Similar to the case presented, the definite histo-pathological diagnosis could only be found in a specimen of sufficient size [6].

Also, due to the rarity of this condition, the consultation of a pathology reference service with major experience in soft-tissue tumors is recommended.

Most patient suffering from malignancy tend towards developing thrombosis. The risk of a venous thromboembolism in such patients has been shown to be seven times higher in these patients [7], [8].

Thrombophilia is also known in KTS, although there are reports of increased risk of bleeding due to disseminated intravascular coagulation in the literature [9], [10].

Coagulation disorders leading to haemorrhage or thromboembolism are also seen in many other conditions. Due to its in-vitro display of clot formation, RTE can be used to assess both the underlying disorders in thrombophilia as well as haemorrhage and therefore allow to draw therapeutically relevant conclusions [11].

In the ROTEM-Analyzer® used in our hospital (TEM International, Munich, Germany) a whole blood sample is given into a cup housing a rotating pin. Under activation of either the extrinsic or intrinsic coagulation the formation of a thrombus is initiated. In addition, thrombocyte function can be blocked, in order to assess the sole contribution of fibrinogen to the clot.

The resulting thrombus is then continuously measured, resulting in various parameters to be recorded.

Coagulation time is defined as the time required from activation until the first sign of clot formation can be detected. Clot formation time (CFT) is the amount of time the clot requires to reach a diameter of 20 mm. The α-angle describes the kinetics of the clot formation, while the maximal clot firmness (MCF) represents the highest achieved diameter of the clot measured in mm. It is dependant on the amount of thrombocytes and their function as well as the concentration of fibrinogen, among others [12].

An increased coagulatory response therefore results in a larger diameter of the clot (MCF) or an increased α-angle. In hyperfibrinolysis however, clot starts to decrease in diameter after a few minutes until is nearly completely dissolved, resulting in the typical pollywog-shape (Figure 5 [Fig. 5]).

At this point in time, RTE is the only reliable test available to determine hyperfibrinolysis as the cause for haemorrhage. This allows for a targeted therapy using inhibitors of fibrinolysis, such as tranexam acid. Tranexam acid is a synthetic derivate of the amino acid lysine, which binds to plasminogen, thus blocking its interactions with fibrin and prevents thrombolysis [13].

RTE is now widely used in trauma and intensive care [14]. It has also found application in patients with disseminated intravascular coagulation as seen in septic patients, among others [15].

As a matter of principle, all precautions to manage haemorrhage or thrombosis should be taken preoperatively (advanced coagulation screening including factor disorders, preparation of blood products) especially in patients with a history of risk factors.

But even despite meticulous preparation, bleeding or thrombosis can occur. In such acute events, the point-of-care availability and real-time display of results of the RTE can be a significant advantage. In addition, since RTE summarizes the coagulatory cascade, it takes into account not only individual factors (most of which are not routinely measured) but also their interactions.

Using RTE, both a preoperative screening for coagulatory disorders as well as their acute presentation can be performed, allowing for a targeted therapy.

As illustrated in this case report, RTE can be possibly applied in a variety of plastic surgery settings.

This is not limited to patients with malignancies. Recently it was shown that RTE might also be able to predict thromboembolic complications in reconstructive microsurgery [16].


Conclusion

RTE provides a fast and inexpensive addition to the routinely performed coagulation work-ups.

It can provide valuable information about the underlying disorders in hypo- and hypercoagulable states of different origins, allowing for targeted therapies.

In patients with a medical history of coagulatory disorders, malignancies or as a preoperative assessment for patients undergoing free tissue transfer, RTE should be strongly considered as an additional tool.


Notes

Competing interests

The authors declare that they have no competing interests.


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