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Anesth Analg 2000;90:1372
© 2000 International Anesthesia Research Society

CRITICAL CARE AND TRAUMA

Fechtner’s Syndrome: Considerations of Anesthetic Management

Fritz Mertzlufft, MD, PhD*, Andreas Koster, MD§, Helmut Steinhart, MD, PhD{dagger}, Joachim F. Schenk, MD{ddagger}, and George J. Crystal, PhD

Departments of *Anesthesiology and Intensive Care, {dagger}ENT Surgery, and {ddagger}Clinical Hemostaseology and Transfusion Medicine, Universitaetskliniken des Saarlandes, Homburg/Saar; §Department of Anesthesiology, Deutsches Herzzentrum Berlin, Berlin, Germany; and ¶Department of Anesthesiology, Illinois Masonic Medical Center and Departments of Anesthesiology and of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, Illinois

Address correspondence and reprint requests to Prof. Dr. med. Fritz Mertzlufft, Klinik fuer Anaesthesiologie und Intensivmedizin, Universitaetskliniken des Saarlandes, D-66421 Homburg/Saar, Germany. Address e-mail to mertzlufft{at}t-online.de


   Abstract
Top
 Abstract
Introduction
 Case Report
 Discussion
 References
 

Implications: Fechtner’s syndrome is a rare form of macrothrombocytopenia (potentially associated with other hemostatic deficiencies, e.g., von Willebrand’s disease and protein Z deficiency), which can exacerbate the risk of uncontrollable bleeding during surgery. We describe the management of a patient with Fechtner’s syndrome involving desmopressin, prednisone, and platelets, which produced safe and effective results during cochlear implant surgery.


   Introduction
Top
 Abstract
 Introduction
Case Report
 Discussion
 References
 
Fechtner’s syndrome (FS) (1–8), the May-Hegglin anomaly (9–11), and the Sebastian platelet syndrome (12–14) are three rare forms of hereditary (autosomal dominant) thrombocytopenia (platelet number usually 20–120 x 103/µL), associated with "giant platelets" (mean volume > 20 fL) and leukocyte inclusions. All three of these conditions can be the cause of bleeding in the absence of an apparent reason (1–5,9–15).

FS was first described in 1985 (1) and has been identified in six families (1–5,8) and may be reported in four other families (6,7). The condition is considered a variant of Alport’s syndrome (1–3,5) because it demonstrates similar symptoms (16–18) [those which are not characteristic of Sebastian platelet syndrome (5,12–14)]. The hematological abnormalities during FS are similar to those during May-Hegglin anomaly (3,9–11). Although often asymptomatic and diagnosed accidentally, FS can be associated with easy bruising, bright variation in bleeding time, renal impairment, hearing loss, eye abnormalities, macrothrombocytopenia (platelet volume 15–20 fL; platelet count 20–>100 x 103/µL), and leukocyte inclusions. Such manifestations can be evident in varying combinations in different members of the same family (1–5). Unexplained bleeding may be observed during FS, despite normal platelet function and survival time (1–5).

Even relatively nonsymptomatic patients with FS may pose a problem when being prepared for surgery, particularly if the procedure augments bleeding or if anticoagulation could be necessary. We report the perioperative management of a patient with FS in whom a history of type I and IV hypersensitivities, including natural rubber latex and silicone, were an additional source of concern.


   Case Report
Top
 Abstract
 Introduction
 Case Report
Discussion
 References
 
A 39-year-old woman (weight, 56 kg; height, 160 cm; ASA physical status III, New York Heart Association classification I) was scheduled for elective cochlear implant surgery (right ear) because of sensorineural high-tone deafness with progressive affection of lower frequencies.

On admission, the patient displayed signs suggestive of FS, e.g., progressive visual loss, recurrent urogenital infections, recurrent micro- and macrohematuria, hemorrhagic diatheses of unexplained origin, decreased platelet counts covering the range 11–28 x 103/µL, variation in bleeding time (3–>15 min), and a deafness since childhood (Table 1). The patient revealed a history of similar symptoms in several family members (Table 1).



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  		Table 1 Findings in a PatientAffected with Fechtner's Syndrome (FS) Undergoing Elective CochlearImplant Surgery

 
The diagnosis of FS was supported by additional findings (1–5) (Table 1), i.e., macrothrombocytopenia (platelet count 12 x 103/µL, mean platelet volume 25 µm3), leukocyte inclusions, and a markedly prolonged bleeding time (>15 min) in the presence of normal values for activated partial thrombin time (aPTT = 28 s), thrombin time (16 s), prothrombin time (PT = 100%), and fibrinogen (215 mg/dL).

Because the medical records of the patient showed a history of multiple surgeries, associated with uncontrollable bleeding, recurrent thromboembolism, and human leuco-cyte antigen (HLA) alloimmunization (Table 1), other potential causes of thrombocytopenia and bleeding diatheses were also analyzed (Table 1). Pseudothrombocytopenia, heparin-induced thrombocytopenia type II, and a deficiency of factor VIII (despite normal values for the aPTT) were precluded (Table 1), whereas decreased concentrations of the von Willebrand factor antigen (vWF:Ag,VIIIR:Ag = 36%) and the von Willebrand activity (ristocetin cofactor = 49%) (Table 1) presently indicated concurrent von Willebrand’s disease, which was identified as type I by using multimeric qualitative analysis.

Further laboratory testing was performed to identify additional hemostaseological disorders, which could have aggravated the bleeding diatheses (Table 1). These included analysis of protein Z, i.e., a vitamin K-dependent glycoprotein, which is synthesized in the liver and interacts with thrombin (19,20). Although rare and of unknown origin, protein Z deficiency has been reported in conjunction with both a borderline decrease of the von Willebrand factor and striking bleeding in otorhinolaryngology surgery (20). The findings obtained in these additional tests demonstrated (Table 1): 1) increased levels for platelet factor 4, d-dimers, serotonin, and thrombin-antithrombin complexes; 2) inhibited spontaneous platelet aggregation and slightly reduced platelet aggregation induced by ADP, collagen, and ristocetin; 3) reduced platelet function (thromboelastrography); and 4) a slightly reduced value (900 ng/mL) for protein Z, indicating protein Z deficiency. Biochemical variables (e.g., hematocrit, pH, base excess) were normal, except for an increased serum creatinine (1.9 mg/dL).

The history of concurrent type I and type IV hypersensitivities (Table 1) prompted biological hypersensitivity testing, which confirmed the reported allergies to penicillin, natural rubber latex, and silicone.

Anesthetic Management
Before surgery, four units of crossmatched platelets were prepared and exposed to ultraviolet irradiation. Prednisone, 30 mg/day IV, was administered for three days according to departmental standards to inhibit the reticuloendothelial system and to reduce the risks arising from the alloimmunization of the patient.

Desmopressin, 0.4 µg/kg IV, was combined with close monitoring of platelet count, bleeding time, and ristocetin cofactor to improve platelet function and increase the expression of the von Willebrand factor.

The decreased platelet count (15 x 103/µL [citrated platelet-poor plasma {PPP}]; 21 x 103/µL [EDTA]), the prolonged bleeding time (>15 min according to Mielke/Ivy), a normalized concentration of the ristocetin cofactor (125%), and normal coagulation of the blood (fibrinogen 221 mg/dL; aPTT 27 s; PT 98%; TT 16 s) after the administration of desmopressin, prompted transfusion of one unit of pretreated platelets, which was performed by using leukodepletion via filter (PL 100 KLE; Pall, Dreieich, Germany). The platelet count (32 x 103/µL [citrated PPP]; 42 x 103/µL [EDTA]) and the bleeding time (9 min) 1 h after the transfusion of the first unit of platelets prompted transfusion of a second unit of the platelets. This normalized the platelet count (50 times 103/µL [citrated PPP]; 55 x 103/µL [EDTA]) and bleeding time (4 min), whereas PT (100%), aPTT (28 s), fibrinogen (313 mg/dL), and ristocetin cofactor (160%) remained stable.

Antiallergic precautions were used, including latex- and silicone-free equipment (with a specially prepared silicone-free cochlear implant), tight coordination among the medical personnel, warmed infusions (37°C), and prednisolone sodium-succinate (250 mg IV). According to departmental standards, lidocaine (100 mg) supplemented by H1 (diphenhydramine, 30 mg) and H2 (ranitidine, 50 mg) blockers were administered IV to attenuate potential reflex- or allergen-induced sequelae.

The induction of anesthesia was accomplished by using midazolam (3 mg IV), propofol (130 mg IV), fentanyl (0.1 µg IV), remifentanil (0.50 µg · kg-1 · h-1), and rocuronium (0.6 mg/kg IV, monitored via train-of-four peripheral nerve stimulation). Arterial (20-gauge) and trilumen central venous catheters (8.5-gauge) were inserted with an endotracheal tube (6.5 Ch), a stomach tube (16 Ch), an esophageal temperature probe, and a urinary catheter (14 Ch). All flushing solutions and instruments were heparin-free. Anesthesia was maintained by using propofol (100 mg · kg-1 · h-1) and remifentanil (0.25 µg · kg-1 · h-1), while performing artificial normocapnic (PETCO2 38–40 mm Hg) ventilation with 30% oxygen in 70% ambient air (low-flow; Cato circle circuit; Dräger, Lübeck, Germany).

Surgery was performed in the dorsal recumbent position by using moderate head turning and support of the head via foam rubber cushion.

During surgery, systemic arterial blood pressure ranged from 122/73 to 104/52 mm Hg, and heart rate remained at approximately 65 bpm. Tidal volume and respiratory frequency were maintained at 490 mL and 10 breaths/min, respectively. Airway pressures remained in the range 11/10/1–14/8/2 cm H2O, and pulse oxymetric O2 saturation and end-tidal PCO2 were stable (98%–99%, and 37–41 mm Hg, respectively). Central venous pressure remained at approximately +9 mm Hg. IV fluid replacement consisted of five units (500 mL) of a cristalloid solution. Electrical stimulation tests at the end of surgery, i.e., after 325 min, indicated functionality of the cochlear implant (Nucleus, Sydney, Australia).

Weaning from anesthesia was uneventful. Total urine output was 1500 mL, and blood loss was 250 mL. Electrolytes, lactate, hemoglobin concentration, pH, PCO2, PO2, and coagulation variables remained within normal ranges for the ensuing 24 h, whereas the serum creatinine concentration was slightly decreased (1.4 mg/dL). No bleeding, thromboembolic events, or allergic reactions were observed during the entire duration of hospitalization. The patient did not require additional platelets. She completely recovered within two days, and for the first time, she was able to hear her children. She was discharged uneventfully within 14 days


   Discussion
Top
 Abstract
 Introduction
 Case Report
 Discussion
References
 
This case report describes the successful management of a patient who has FS, as diagnosed from clinical signs and laboratory findings in the patient herself and family members (1–5) (Table 1).

The decrease in platelet count associated with FS may not be as severe as in the present case (12 x 103/µL) (1–5,15). However, if clinical manifestations of FS are present either in the patient or a member of the family, even a less pronounced thrombocytopenia (e.g., 50–70 x 103/µL) should prompt FS-related laboratory testing (platelet volume, platelet morphology, bleeding time) (Table 1) and analysis for coexisting hemostatic disorders (e.g., pseudothrombocytopenia and other causes of thrombocytopenia and bleeding diatheses).

Remarkably, FS was associated with two other rare bleeding abnormalities, i.e., von Willebrand’s disease (type I) and protein Z deficiency (Table 1). It is not known whether these latter abnormalities are attributable to FS (1–5,15,20) or are independent phenomena. Further investigation is required to determine the significance of the increased incidence of thromboembolic events (Table 1) in the FS patient of this study, including genetic and ultrastructural analysis.

The patient’s HLA alloimmunization and history of poor response to single-donor and HLA-matched platelets are likely the result of the multiple platelet transfusions (21–24) given during previous operations (Table 1).

The measures that we used to minimize FS-associated risks were based on a treatment proposed in relation to hemostatic defects and bleeding disorders and on principles of transfusion medicine (21–24). Cryoprecipitate was precluded because of the known high risk of viral exposure. Fresh frozen plasma has been suggested as a means to increase von Willebrand factor antigen (as well as factor VIIIR:C activity) and to normalize bleeding time. However, this was eliminated because of the patient’s history of renal disorders and the increase in serum creatinine (1.9 mg/dL) (Table 1). Humate-P intermediate-purity concentrate was considered if desmopressin had failed to enhance hemostasis. Crossmatched platelets were used because of the history of HLA alloimmunization and poor response to single-donor and matched platelets (22–24). In keeping with the literature (21–24), both leukodepletion and ultraviolet irradiation were performed to prevent further transfusion-related reactions.

We used nonheparin bonded instrumentation because the patient had experienced multiple surgeries, which occasionally had involved thrombosis prophylaxis by using unfractionated heparin. The latter has been shown to cause thromboembolism, drops in platelet count, and significant bleeding per se, i.e., in case of heparin-induced immunological thrombocytopenia (HIT type II) (25), particularly in case of reexposure to heparin (25,26). Although no free platelet-reactive antibodies were identified in this patient (Table 1), this was possibly because antibody concentration had decreased by the time the measurement was obtained (25,26).

We chose the instrumentation and monitoring used in this case because of the multiple complicating factors involved, including FS, extended surgical duration (more than five hours) involving complex preparation in close proximity to arteries and uncollapsible veins, and various allergies, which may have required emergent intravascular volume expansion, transfusion, vasoactive medication, and other life-support techniques. However, such invasive instrumentation may not be necessary in all surgical patients affected with FS.

In conclusion, we describe herein the management of a patient with FS involving desmopressin, prednisone, and transfusion of platelets, which produced safe and effective results during cochlear implant surgery. This protocol prevented excessive bleeding, thromboembolic formation, and anaphylactic reactions, and it reduced the need for transfusion of blood products. Our technique of patient management may be an option in patients with FS undergoing other types of surgery.


   References
Top
 Abstract
 Introduction
 Case Report
 Discussion
 References
 

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Accepted for publication February 29, 2000.





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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 2000 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press