Microsurgical Breast Reconstruction in Patients with Disorders of Hemostasis: Perioperative Risks and Management

Background:

Surgical and technological advances have resulted in the widespread adoption of microsurgical breast reconstruction. Many comorbidities that potentially might impair vasculature and wound healing are no longer considered contraindications for these procedures. However, some uncertainty still prevails regarding the perioperative management of patients with disorders of hemostasis.

Methods:

The authors combined a literature review with a retrospective chart review of patients with disorders of hemostasis who had undergone microsurgical breast reconstruction at the senior author’s (J.F.) center between 2015 to 2020. Several disorders associated with thrombotic and/or hemorrhagic complications were identified, and a standardized risk assessment and management strategy was developed in cooperation with a hematologist.

Results:

Overall, 10 studies were identified comprising 29 patients who had a defined disorder of hemostasis and underwent microsurgical breast reconstruction. Seventeen microsurgical breast reconstructions were performed on 11 patients at the senior author’s (J.F.) center. High factor VIII levels, heterozygous factor V Leiden, and heterozygous prothrombin mutation G20210A were the most common genetic or mixed genetic/acquired thrombophilic conditions. As expected, hereditary antithrombin, protein C, or protein S deficiencies were rare. Among hemorrhagic disorders, thrombocytopenia, platelet dysfunction, and von Willebrand disease or low von Willebrand factor levels were those factors most frequently associated with increased perioperative bleeding.

Conclusions:

Patients should be screened for elevated risk of thrombosis or bleeding before undergoing microsurgical breast reconstruction, and positive screening should prompt a complete hematologic evaluation. Interdisciplinary management of these disorders with a hematologist is essential to minimize risks and to obtain optimal reconstructive results.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, IV.

With surgical and technological improvements, microsurgical breast reconstruction has become the standard following mastectomies for breast cancer.^1,2 In many centers, comorbidities that impair vasculature and wound healing, such as obesity or diabetes mellitus, are no longer considered contraindications for such procedures.^3,4 However, the perioperative diagnosis and management of disorders of hemostasis remain a matter of uncertainty. Thrombophilic conditions increase the risk of perioperative thromboembolism, and hemorrhagic diatheses are associated with an increased risk of microvascular bleeding, hematomas, and impaired wound healing.

In patients without disorders of hemostasis, the incidence of microvascular anastomotic venous and arterial thrombosis has been reported to be 1.5 percent and 0.6 percent, respectively, with respective flap loss rates because of venous and arterial anastomotic thrombosis of 26.7 percent and 11.1 percent.⁵ Postoperative hematomas are the second most common cause of free flap reexploration in patients without known disorders of hemostasis.⁶ Increased intraoperative bleeding extends the operation time, especially during flap dissection, when visibility of the operative field is paramount to avoid injury of small perforating branches and neighboring structures.⁷

Because venous thromboembolism including microvascular thrombosis and even minor bleeding can jeopardize the success of microsurgical breast reconstruction, we aimed to identify every potentially relevant thrombophilia and hemorrhagic disease and include them in our risk stratification.^8,9 The aims of this review are to provide (1) a standardized perioperative procedure for the identification and management of clinically relevant disorders of hemostasis, and (2) a combined literature and chart review of microsurgical breast reconstruction in patients with disorders of hemostasis.

STANDARD PERIOPERATIVE APPROACH

The standard perioperative procedure for the described patients treated at the senior author’s (J.F.) center involved a standardized history and basic laboratory tests including complete blood cell count, prothrombin time, activated partial thromboplastin time, and fibrinogen. Additional specific hemostasis tests to detect any corresponding disorders were performed by a hematologist as part of the consultation. When disorders of hemostasis were diagnosed, patients received appropriate treatment before microsurgery was performed. If necessary, perioperative measures were carried out as suggested by the hematologist. Where no disorders of hemostasis were discovered, standardized venous thromboembolism prophylaxis was routinely started 6 hours postoperatively, using subcutanesous nadroparin (Fraxiparine; Aspen Pharma Schweiz GmbH, Baar, Switzerland) once daily. The dose was weight dependent [<50 kg body weight, 0.2 ml (1900 U); 50 to 70 kg body weight, 0.3 ml (2850 U); 70 to 100 kg body weight, 0.4 ml (3800 U); and >100 kg body weight (0.6 ml (5700 U)]. Antibiotic prophylaxis was started 30 minutes before surgery using intravenous cefazolin (Kefzol; Teva Pharma AG, Zug, Switzerland) 2 g, and continued until postoperative day 3. Computed tomographic angiography was performed for perforator mapping and preoperative planning in all patients. All flaps were dissected in an identical fashion by the senior author. Arteries were hand-sewn, and veins were anastomosed using a venous coupling device (Synovis, Inc., Birmingham Ala.). The donor site was closed in standard fashion over closed suction drains, and the flaps were inset to restore the breast footprint over drains as well. Drains were removed when output was less than 30 ml over 24 hours. Fluid management was goal-directed to maintain systolic blood pressure above 100 mmHg. Postoperative monitoring was performed at regular intervals.¹⁰ Parameters included color and temperature of the skin monitor island and Doppler signal. If flap perfusion was questionable, indocyanine green fluorescence angiography was performed.¹¹ All patients wore compression stockings, and mobilization was initiated on postoperative day 1.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Given the case series nature of this publication, no approval by the ethics board of our corresponding institution is required.

STANDARDIZED PROCEDURE FOR THE PREOPERATIVE DIAGNOSIS AND PERIOPERATIVE MANAGEMENT OF THROMBOPHILIC CONDITIONS

There is currently no consensus on the optimal screening and management strategy for thrombophilic conditions in patients undergoing microvascular breast reconstruction.^12–18 Although previous recommendations have not supported routine screening, more recent studies have advanced several reasons for more aggressive screening protocols.^14,19 Perioperative hematologic management can help to minimize complications associated with some thrombophilic conditions.¹² If a severe thrombophilic disorder can be identified preoperatively, an alternative type of reconstruction such as a pedicled flap might be considered to avoid unnecessary reoperations because of microvascular thromboses. The potential psychological trauma after a total flap loss is also a factor to be considered, especially given the low salvage rates in patients with a hypercoagulable condition.^12,16

Thrombophilic conditions are evident risk factors for initial venous thromboembolism and weaker risk factors for recurrence. However, thrombophilia testing remains controversial because evidence-based therapeutic consequences have not been established, and because it has been supposed to be not cost-effective.^20,21 Some reviews on the clinical significance of thrombophilia screening recommend restricting the indications for testing, referencing studies that did not find any influence of thrombophilic conditions on the rate of venous thromboembolism or on the type and duration of prophylaxis or treatment.^22,23 Other large studies, however, have shown that thrombophilia significantly increases the risk of first and recurrent venous thromboembolism and that it should be included in the risk stratification.^24–28

Our indications for thrombophilia screening are based on clinical data, the patient’s medical history, including family history recorded on a standardized questionnaire, and on the recommendations of an international expert committee.^{12,16,18,29,30} (See Document, Supplemental Digital Content 1, which shows the exemplary screening questionnaire for thromboembolism, http://links.lww.com/PRS/F346.) A hematologist was involved when thrombophilia screening was indicated based on the patient’s history, and when the corresponding laboratory screening had to be arranged and interpreted. One earlier study had shown that multidisciplinary care and management involving a hematologist in hypercoagulable patients had a positive correlation with improved flap outcomes, although this did not reach statistical significance (p = 0.064).¹⁹

Many study groups limit thrombophilia screening to factor V Leiden mutation; prothrombin mutation G20210A; the inhibitors antithrombin, protein C, and protein S; and possibly to the autoantibodies to detect antiphospholipid syndrome. This approach ignores several clinically relevant thrombophilic conditions that, especially in combination, may substantially increase the risk of venous thromboembolism. The prevalence of factor V Leiden; prothrombin mutation G20210A; antithrombin, protein C, and protein S deficiency in the general population is low; whereas increased factor VIII levels, hyperhomocysteinemia, increased lipoprotein(a), and sticky platelet syndrome are relatively common (Table 1).^31–41 Our complete thrombophilia screening includes factor V Leiden; prothrombin mutation G20210A; antithrombin; protein C; protein S; protein Z; clottable and total fibrinogen; levels of factors VIII, IX, and XI; homocysteine; lipoprotein(a); sticky platelet syndrome; and antiphospholipid syndrome screening consisting of lupus anticoagulant and anticardiolipin and anti–β2-glycoprotein I (β2GPI) antibodies types immunoglobulin G and immunoglobulin M (Fig. 1).^15,42,43 The quality of thrombophilia screening depends crucially on several conditions, to which we strictly adhered, but which have been insufficiently considered in many studies or not at all. Except for the molecular genetic analysis of factor V Leiden and prothrombin mutation G20210A, the assays have extremely different sensitivities and specificities for the detection of a respective deficiency, and different demands on preanalytical conditions. The prevalence of a thrombophilic condition also depends on the choice of the correct reference range. A positive result must be checked against a second examination at another point in time. If a reduced antithrombin, protein C, or protein S level is confirmed, molecular genetic analysis of the corresponding gene must be carried out to identify whether a mutation is present.

Table 1.

Prevalence, Risk of First and Recurrent Venous Thromboembolism, and Risk of Arterial Thromboembolism in Hereditary Thrombophilic Conditions

Condition	Prevalence in the General Population (%)*	Prevalence in Patients with VTE%†	Risk of First VTE		Risk of VTE Recurrence		Risk of Arterial Thrombosis
			OR (95% CI)‡	p	OR (95% CI)§	p	OR (95% CI)∥	p
FVL heterozygous	5¶	20	5.0 (4.6–5.5)	<0.00001	1.5 (1.1–2.1)	0.005	1.17 (1.08–1.28)	0.03
PTM heterozygous	3	10	3.1 (2.1–3.4)	<0.00001	1.4 (0.9–2.2)	0.08	1.31 (1.12–1.52)	0.02
AT deficiency	0.02	1	16.2 (9.9–26.7)	<0.00001	3.6 (1.4–8.9)	0.006	1.2 (0.1–11.3)	0.89
PC deficiency	0.2	3	7.5 (3.2–17.5)	<0.0001	2.9 (1.4–6.0)	0.03	8.4 (2.3–30)	0.001
PS deficiency	0.3	2	5.3 (2.7–10.6)	<0.0001	2.5 (0.8–7.1)	0.08	5.7 (1.4–22.8)	0.02

VTE, venous thromboembolism; FVL, factor V Leiden; PTM, prothrombin mutation G20210A; AT, antithrombin; PC, protein C; PS, protein S.

^*Rosendaal FR. Venous thrombosis: A multicausal disease. Lancet 1999;353:1167–1173; Hotoleanu C. Genetic risk factors in venous thromboembolism. Adv Exp Med Biol. 2017;906:253–272.

^†Di Minno MN, Ambrosino P, Ageno W, Rosendaal F, Di Minno G, Dentali F. Natural anticoagulants deficiency and the risk of venous thromboembolism: A meta-analysis of observational studies. Thromb Res. 2015;135:923–932.

^‡Di Minno MN, Ambrosino P, Ageno W, Rosendaal F, Di Minno G, Dentali F. Natural anticoagulants deficiency and the risk of venous thromboembolism: A meta-analysis of observational studies. Thromb Res. 2015;135:923–932; Gohil R, Peck G, Sharma P. The genetics of venous thromboembolism: A meta-analysis involving approximately 120,000 cases and 180,000 controls. Thromb Haemost. 2009;102:360–370.

^§Di Minno MN, Ambrosino P, Ageno W, Rosendaal F, Di Minno G, Dentali F. Natural anticoagulants deficiency and the risk of venous thromboembolism: A meta-analysis of observational studies. Thromb Res. 2015;135:923–932; Segal JB, Brotman DJ, Necochea AJ, et al. Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: A systematic review. JAMA 2009;301:2472–2485.

^∥Mahmoodi BK, Brouwer JL, Veeger NJ, van der Meer J. Hereditary deficiency of protein C or protein S confers increased risk of arterial thromboembolic events at a young age: Results from a large family cohort study. Circulation 2008;118:1659–1667; Ye Z, Liu EH, Higgins JP, et al. Seven haemostatic gene polymorphisms in coronary disease: Meta-analysis of 66,155 cases and 91,307 controls. Lancet 2006;367:651–658.

^¶In White people.

Fig. 1.

Simplified screening algorithm for hemorrhagic or thrombophilic disorders. Note that no laboratory screening test exists for thrombophilic disorders. CBC, complete blood cell count; APTT, activated partial thromboplastin time; PT, prothrombin time; VTE, venous thromboembolism; APC, activated protein C resistance; Ig, immunoglobulin.

Many patients with thrombophilic conditions are asymptomatic or only become symptomatic when they occur in combination with one another or in combination with acquired or environmental risk factors.^35,44–46 Obesity, advanced age, and chronic lung disease number among the factors that have been associated with elevated thrombotic risk in microsurgical breast reconstruction.⁴⁷ Patients with breast cancer undergoing reconstructive procedures fall into a high-risk group in terms of venous thromboembolism.⁴⁸ Breast cancer treatment is associated with a 2.5-fold risk of venous thromboembolism, mainly caused by chemotherapy, including estrogen receptor modulation (tamoxifen or raloxifene), and the malignancy itself, all of which may be accompanied by a procoagulant state.^49,50

The type of microsurgery may also augment the total risk of venous thromboembolism. The perioperative risk of thrombosis increases with the duration of surgery (especially >4 hours), postoperative immobilization, and tissue traumatization.^48,51 When deep inferior epigastric perforator (DIEP) reconstruction was used, increased intraabdominal pressure with tightening of the abdominal fascia and improper postoperative abdominal binder placement have been associated with venous thromboembolism.^48,52 Although some reconstructive microsurgeons consider thrombophilia to be an absolute contraindication for microvascular free flap reconstruction, we believe that a hemostatic disorder should not generally exclude a patient from microsurgery. However, the patient must be informed about possible intraoperative problems, and a backup plan should be prepared preoperatively.⁵³ It is difficult to pinpoint the precise cause of an anastomotic thrombosis or flap loss in any microvascular free tissue transfer because many of these complications are likely multifactorial.^15,30 Considering that technical error is the most common cause of microvascular failure, a meticulous surgical technique is particularly important in patients with disorders of hemostasis.⁵⁴ Strategies to manage intraoperative anastomotic thrombosis or bleeding have also been described previously.^15,55,56

Several risk assessment models have been developed and validated to optimize primary perioperative thromboprophylaxis. The Caprini model is the most widespread of these and considers thrombophilic conditions in risk stratification.^57–60 Our risk assessment model is based on the Caprini strategy and has been tailored to the specific conditions of microsurgical breast reconstruction (Table 2).^57–65 For a more precise differentiation of the risks from previous thromboembolism and thrombophilic conditions, the concept of a French working group was considered that had been developed originally for the optimization of venous thromboembolism prophylaxis in pregnancy.^61,62 We used more recent recommendations to differentiate more precisely the risk of thromboembolism in antiphospholipid syndrome based on different laboratory constellations.^63–65 When risk scores exceeded 8, the drug-based venous thromboembolism prophylaxis was modified in consultation with a hematologist, taking into account the specific individual risk of bleeding (Table 3).⁶⁶

Table 2.

Venous Thromboembolism Risk Assessment Model for Microsurgical Breast Reconstruction

	Score
Previous thromboembolism
Permanent anticoagulation because of VTE, ATE, AF, artificial devices	10
Previous PE or proximal DVT	5
APS, LA positive or triple positive (LA + anti-CLP + anti-β2GPI)	5
APS and previous ATE, irrespective of laboratory constellation	5
Stroke < 1 mo	5
APS, anti-CLP + anti-β2GPI positive	3
APS, anti-CLP or anti-β2GPI	2
One distal DVT	2
Positive family history of VTE in first-degree relatives	2
Other clinical condition
Age 40–59; 60–74; ≥75 yr	1; 2; 3
Major surgery >45 min	2
Malignancy, present or previous	2
Obesity (BMI > 30 kg/m2), immobilization	1 each
Varicose veins, postthrombotic syndrome	1 each
Congestive heart failure, severe lung disease, renal insufficiency	1 each
IBS, rheumatic disorders, inflammation	1 each
Estrogens or estrogen receptor modulators	1
Recurrent spontaneous abortion (≥3), late placental complications	1 each
Hereditary or mixed thrombophilic condition
Antithrombin deficiency, except type II HBS mutations	6
Homozygous FVL or homozygous PTM or compound heterozygous FVL + PTM	5 each
Protein C or protein S deficiency	4 each
Heterozygous FVL or heterozygous PTM or protein S Heerlen	3 each
Antithrombin deficiency type II HBS, or acquired antithrombin deficiency	2
Dysfibrinogenemia, depending on the mutation type	1–5
Elevated factor VIII	2
Elevated factor IX or factor XI, high lipoprotein(a)	1 each
Hyperhomocysteinemia, protein Z deficiency, sticky platelet syndrome	1 each

VTE, venous thromboembolism; ATE, arterial thromboembolism; AF, atrial fibrillation; PE, pulmonary embolism; DVT, deep vein thrombosis; APS, antiphospholipid syndrome; LA, lupus anticoagulant; CLP, cardiolipin; β2GPI, β2-glycoprotein I; BMI, body mass index; IBS, irritable bowel syndrome; HBS, heparin-binding site; FVL, factor V Leiden; PTM, prothrombin mutation G20210A;

*Modified according to Caprini, 2005⁵⁷; Chauleur et al., 2010 and 2018^61,62; Garcia and Erkan, 2018⁶³; and Pengo et al., 2015 and 2018.^64,65

Table 3.

Strategy for Prophylaxis and Therapy of Thromboembolism and Considerations for Therapeutic Safety

Score 4–6

Nadroparin, body weight adapted: <50 kg, 0.2 ml (1900 U); 50–69 kg, 0.3 ml (2850 U); 70–99 kg, 0.4 ml (3800 U); ≥100 kg, 0.6 ml (5700 U); start 6 hr postoperatively, continue over 5 days

Score 7–8

Extend prophylaxis to 7–10 days

Score 9–10

Increase nadroparin dose (e.g., 0.4 ml instead of 0.3 ml in patients weighing 50–69 kg; extend prophylaxis until complete mobilization and complete subsidence of an inflammation

Score >10

Continue with semitherapeutic or full therapeutic anticoagulation postoperatively; possibly add aspirin perioperatively

Factors associated with increased bleeding*

• Age and female sex

• Impaired renal function

• History of bleeding

• Hemostatic disorder including thrombocytopenia

• Antiplatelet agents, including NSAIDs

NSAIDs, nonsteroidal antiinflammatory drugs.

^*Modified according to Gombotz H, Knotzer H. Preoperative identification of patients with increased risk for perioperative bleeding. Curr Opin Anaesthesiol. 2013;26:82–90.

STANDARDIZED PROCEDURE FOR THE PREOPERATIVE DIAGNOSIS AND PERIOPERATIVE MANAGEMENT OF HEMORRHAGIC DISORDERS

Bleeding assessment tools for the standardization and interpretation of a bleeding history offer a complete and structured interview, but their diagnostic value for the detection of a mild bleeding disorder is limited.⁶⁷ In contrast, laboratory screening alone cannot cover all clinically relevant hemorrhagic disorders, and specific laboratory analysis to exclude these disorders in all patients is not cost-effective.⁶⁸ We have developed an approach that combines a standardized questionnaire, clinical examination, and laboratory screening (Fig. 1). The bleeding score was established by 10 experienced clinical hematologists. (See Table, Supplemental Digital Content 2, which shows the standardized questionnaire to determine a bleeding tendency, http://links.lww.com/PRS/F347.) Arbitrary scores were assigned to the various bleeding symptoms. If there was a high probability of an association between a bleeding symptom and a hemorrhagic diathesis, the scores were higher than if the probability was lower. For example, increased bleeding after tooth extraction was assigned a higher score than frequent nosebleeds. In contrast to the International Society on Thrombosis and Haemostasis Bleeding Assessment Tool, there was no differentiation of the bleeding symptoms into different degrees of severity.⁶⁹ An overall score greater than 3 indicates an elevated bleeding risk and that, after careful reexamination of the patient’s history, a hematology consultation is warranted. This bleeding score was predictive of bleeding in a clinical cohort study on cardiac surgery patients.⁷⁰ The hematologist will also be involved if basic laboratory tests including complete blood cell count, activated partial thromboplastin time, prothrombin time, and fibrinogen are abnormal.^68,71 In the event of a suspicious history or suspicious screening tests, further laboratory analyses are required to exclude a hemostatic disorder. Except for vasculopathies, almost all clinically relevant hemorrhagic disorders can be excluded or detected: thrombocytopenia, platelet dysfunction, coagulopathies including factor XIII deficiency, low von Willebrand factor levels or von Willebrand disease, and hyperfibrinolysis.⁷² For the drugs frequently used in patients with microsurgical breast reconstruction, it should be known whether they can cause platelet dysfunction. Our perioperative management strategy is outlined. (See Table, Supplemental Digital Content 3, which shows hemorrhagic disorders and appropriate perioperative management in microsurgical breast reconstruction, http://links.lww.com/PRS/F348.)

LITERATURE REVIEW

A comprehensive literature search was performed using the electronic databases PubMed (U.S. National Library of Medicine, Bethesda, Md.), EMBASE (Elsevier, Amsterdam, The Netherlands), and Web of Science (Thomson Reuters, New York, N.Y.). Search items included “autologous breast reconstruction,” “microsurgical breast reconstruction,” or “microsurgery” in combination with “hemostatic disorder” or “thrombophilia,” or the respective condition. Publications were eligible for inclusion if they provided information on microsurgical breast reconstruction in patients with disorders of hemostasis. We considered articles published in English and German before June 1, 2020. This included prospective and retrospective clinical studies, review articles, and case reports. No other restrictions were applied. We selected those articles that fulfilled our inclusion criteria and scanned the references of all selected articles to find additional literature related to our research question. At the end of this process, 10 articles were found eligible for our review. Additional articles were consulted for background information regarding disorders of hemostasis and perioperative management.

Overall, 10 studies comprising 29 patients who had a defined thrombophilic disorder and underwent microsurgical breast reconstruction were identified. Thirteen complete flap failures and one partial flap loss were observed in 10 patients. The underlying thrombophilic or hemostatic condition, indication, type of reconstruction, anticoagulation protocol, and complications are presented. (See Table, Supplemental Digital Content 4, which shows a literature review of patients with thrombophilic conditions who underwent microsurgical breast reconstruction, http://links.lww.com/PRS/F349.)

Factor V Leiden was present in 20 patients undergoing microsurgical breast reconstruction and associated with a flap loss rate of 42 percent.^{12,13,15,30,55,73} One patient with prothrombin mutation G20210A underwent successful breast reconstruction with a muscle-sparing transverse rectus abdominis musculocutaneous (msTRAM) and a superficial inferior epigastric artery (SIEA) flap.¹⁹ Elevated factor VIII was present in two patients. One patient also had essential thrombocytosis and antiphospholipid syndrome. The presence of elevated factor VIII was associated with a flap loss rate of 75 percent.^13,19 One patient with hereditary protein C deficiency underwent successful DIEP and SIEA flap breast reconstruction.¹⁹ In contrast, one patient with hereditary protein S deficiency had bilateral loss of msTRAM flaps.¹⁵ In another patient with protein S deficiency, reconstruction with a TRAM flap was uneventful.¹⁴ All patients described in the literature with antiphospholipid syndrome experienced arterial or venous thrombosis and ultimate flap failure (flap loss rate, 100 percent).^12,19,74 We did not find any data regarding microsurgical breast reconstruction in patients with hereditary antithrombin deficiency or sticky platelet syndrome. Also, no reports were identified regarding hemorrhagic disorders.

PATIENT CHART REVIEW

A retrospective review was performed for all patients with disorders of hemostasis who had undergone microsurgical breast reconstruction at the senior author’s (J.F.) center between 2015 and 2020. Types of reconstruction included DIEP, SIEA, or superior gluteal artery perforator flaps. We reviewed patient records regarding preoperative hematologic workup or therapy, operative notes, and hospital course including anticoagulation and flap outcomes. Statistical analysis was performed using MedCalc (version 19.1.6; MedCalc Software, Ltd., Ostend, Belgium). Patient demographic data were summarized using descriptive statistics (mean and range).

Between 2015 and 2020, 17 microsurgical breast reconstructions were performed on 11 patients with disorders of hemostasis. The average age and body mass index was 49 years (range, 40 to 59 years) and 23.5 kg/m² (range, 19.5 to 27.8 kg/m²), respectively. One patient was a current smoker. We observed one flap loss in a patient with mild platelet dysfunction (flap loss rate, 5.9 percent). The underlying hemostatic condition, indication, type of reconstruction, anticoagulation protocol, and complications are presented. (See Table, Supplemental Digital Content 5, which shows a chart review of patients with disorders of hemostasis who underwent microsurgical breast reconstruction at our center, http://links.lww.com/PRS/F350.)

Three patients had a heterozygous factor V Leiden mutation. One patient undergoing a free DIEP flap developed venous thrombosis and needed operative intervention with exploration, thrombectomy, and anticoagulation. The flap was salvaged successfully (Fig. 2). Another patient with a factor V Leiden mutation also had elevated factor VIII levels but had a successful DIEP flap reconstruction combined with a lymph node transfer without adverse events. Two patients with a confirmed prothrombin mutation G20210A underwent successful autologous reconstruction using a free superior gluteal artery perforator and DIEP flap without complications or need for reoperation. None of our patients had protein C or protein S deficiency, antithrombin deficiency, or antiphospholipid syndrome.

Fig. 2.

Intraoperative view of an 8-cm-long venous microthrombus on the left side in a patient with heterozygous factor V Leiden mutation who underwent breast reconstruction with bilateral DIEP flaps.

Some patients had hemorrhagic conditions with increased risk of bleeding and compromised flap perfusion. Three patients had thrombocytopenia and platelet dysfunction. One patient had an uneventful reconstruction, and another developed a hematoma that needed exploration. The third patient unfortunately had total flap loss secondary to a hematoma, followed by arterial thrombosis on the right side. She underwent standard arterial thrombectomy and repeated anastomoses to the internal mammary vessels. However, the flap was not salvageable. Two patients had von Willebrand disease or low von Willebrand factor levels, and both underwent successful reconstruction without complications.

STRENGTHS AND LIMITATIONS

This article presents the largest combined literature and chart review thus far of microsurgical breast reconstruction in patients with disorders of hemostasis. The authors also offer a standardized procedure for the perioperative diagnosis and therapy of these disorders in the setting of microsurgical breast reconstruction.

The present review nevertheless has some limitations. Clinical cases were evaluated retrospectively, and the total number of patients is low. Both the patient chart review and the literature review focused on microsurgical breast reconstruction only to obtain a more homogenous cohort. We did not include free tissue transfer in head and neck reconstruction, lower extremity salvage, or microvascular operations. There is presently no consensus on the optimal perioperative management, and consequently perioperative prophylactic and therapeutic regimens between studies or even between authors within the same study differed.¹⁹

This review was not designed to evaluate anesthetic management. However, the period for thrombosis formation begins with the initiation of anesthesia, and the risk is increased by vasodilatory or vasoconstrictive medication, muscle relaxants, and low body temperature that occurs routinely during surgery.^45,75,76 We did not focus on patients with permanent anticoagulation whose perioperative management has been described elsewhere.⁷⁷ Given the absence of well-designed, randomized, controlled trials, our recommendations wherever possible are evidence-based but sometimes reflect expert opinion.

Finally, our perioperative strategy for the diagnosis and treatment of disorders of hemostasis has not yet been validated. As mentioned, the number of patients with disorders of hemostasis undergoing microsurgical breast reconstruction has been relatively low. Thus, single-center studies might not have the statistical power necessary to demonstrate clinical efficiency.

CONCLUSIONS

The authors present a large, combined literature and chart review of microsurgical breast reconstruction in patients with disorders of hemostasis. Patients should be screened for increased risk of thrombosis or bleeding before undergoing microsurgical breast reconstruction, and a positive screening should prompt a complete hematologic evaluation. Awareness of disorders of hemostasis and interdisciplinary perioperative management with a hematologist are essential to ensure optimal reconstructive results.

PATIENT CONSENT

The patients discussed in this article provided written consent in accordance with institutional policies.