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Clinical Cyanosis in a Patient Presenting for Outpatient Colonoscopy: A Case Report of Hemoglobin Kansas

Varnado-Rhodes, Yael S. MD

doi: 10.1213/XAA.0000000000000959
Case Reports
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Gene mutations that affect the synthesis or structure of hemoglobin are present in 7% of the world’s population. These mutations lead to variant hemoglobinopathies with phenotypes that range from clinically insignificant to fatal. Because monitoring oxygen saturation is standard of care and critical to detecting hypoxemia, it is crucial to recognize factors that might interfere with the measurement of oxygen saturation or decrease oxygen delivery. We discuss the management of a patient who presented to a freestanding surgical center with the rare variant hemoglobin Kansas, clinical cyanosis, and an initial pulse oximetry reading of 68% on room air.

From the Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland.

Accepted for publication November 30, 2018.

Funding: None.

The author declares no conflicts of interest.

Address correspondence to Yael S. Varnado-Rhodes, MD, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Outpatient Center, Johns Hopkins University, c/o Yvette James, 601 N Caroline St, JHOC B165, Baltimore, MD 21287. Address e-mail to yvarnad1@jhmi.edu.

Hemoglobin Kansas is 1 of >1000 known hemoglobin variants.1 This rare hemoglobin variant, first described in 1961 by Reissmann et al,2 causes asymptomatic cyanosis as a result of an asparagine-to-threonine substitution in the β-chain of hemoglobin at position 102 in the fourth residue of the G helix. This single amino acid mutation leads to decreased oxygen affinity and low heme-heme cooperativity, shifting the oxygen dissociation curve to the right (Figure).2 Consequently, patients with hemoglobin Kansas present with cyanosis and decreased oxygen saturation. Hemoglobin Kansas had previously been reported primarily in Japanese families, although cases have been reported in Brazil3 and Turkey.4

Figure.

Figure.

We describe a patient of Caucasian heritage with hemoglobin Kansas who presented to a freestanding ambulatory surgery center for an outpatient colonoscopy. We describe the perioperative management and suggest that, although hemoglobinopathies are rare, they should be considered in the differential diagnosis when patients present with unexpected cyanosis and decreased oxygen saturation as measured by pulse oximetry. The patient provided written informed consent for this case report.

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CASE REPORT

A 61-year-old Caucasian man who had a history of hypertension and hemoglobin Kansas presented to an outpatient surgery center for an elective colonoscopy. We had no information regarding his hemoglobinopathy before his arrival on the day of surgery. He was 5′11″ and 74 kg with a body mass index of 22.6 kg/m2. Preoperatively, his blood pressure was 127/79 mm Hg, his heart rate was 67 beats/min, and his oxygen saturation on room air was 68%, as measured with a pulse oximeter (Welch Allyn, Beaverton, OR). When the preoperative staff noted the low pulse oximeter reading, the patient reported that he “was always blue” because he had hemoglobin Kansas and was followed by the National Institutes of Health. The patient manifested cyanotic signs with bluish fingertips and lips. He also stated that even when he was administered oxygen, his pulse oximeter reading would not increase above 80%.

In the preoperative area, unsuccessful attempts were made to contact the patient’s hematologist at the National Institutes of Health to obtain more information regarding his hemoglobinopathy. The patient stated that he was in his usual state of health and denied any shortness of breath at rest. He reported that his exercise capacity was “good” and he could climb >2 flights of stairs and exercise without chest pain or dyspnea. After a brief review of the hemoglobin Kansas literature online, additional discussion with the patient regarding his medical history, and conferring with the gastroenterologist to verify that the procedure would require <15 minutes, we elected to proceed with the colonoscopy.

In the procedure room, the patient was placed in the left lateral decubitus position and an oxygen mask was placed on his face. While breathing room air, the patient’s oxygen saturation measured by pulse oximetry (Spo2) reading ranged between 68% and 70%. Oxygen was then delivered through the 100% nonrebreather mask at flows of 5, 10, and 15 L/min, which produced Spo2 readings of 78%–80%, 80%, and 80%–83%, respectively. We administered 15 L/min of oxygen and used standard monitors according to American Society of Anesthesiologists guidelines throughout the case.5 In addition, we continuously observed the patient for any changes in his level of cyanosis. As this was a freestanding surgery center, invasive monitors and blood gas analysis were not available.

Sedation was initiated with 100 mg of propofol IV and maintained with intermittent IV propofol boluses. A total of 200 mg of IV propofol was administered during the uneventful 15-minute procedure. The patient remained hemodynamically stable throughout the procedure, and pulse oximetry readings ranged between 80% and 83%. At the conclusion of the procedure, the patient was transferred to the postanesthesia recovery unit awake and talking. In the recovery unit, the oxygen flow to his nonrebreather mask was reduced to 8 L/min of oxygen. The patient’s initial blood pressure was 118/67 mm Hg, heart rate was 72 beats/min, Spo2 was 81%, and respiratory rate was 12 breaths/min. The patient successfully recovered from his procedure and was discharged home with no further sequelae.

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DISCUSSION

Variant hemoglobins are classified by whether they affect the globin protein subunit and cause thalassemias or produce an abnormal globin structure, causing hemoglobin variants including hemoglobin Kansas.6 Most hemoglobin variants are due to missense single amino acid substitutions in the globin protein. The variants are usually benign, but some can cause hemolysis, impaired oxygen binding, secondary polycythemia, and even methemoglobinemia.6 Only 3 known variant hemoglobins have a reduced oxygen affinity and cause clinical cyanosis: hemoglobin Kansas, hemoglobin Saint Mande, and hemoglobin Beth Israel. Each is caused by a different substitution at the same amino acid position.7

The single amino acid mutation of hemoglobin Kansas inhibits formation of the hydrogen bond with Asp 94 that normally stabilizes the oxygenated state of hemoglobin. This instability leads to an increase in the low-affinity deoxygenated state of hemoglobin and reduces heme-heme cooperativity. Reissmann et al,2 who characterized a patient with hemoglobin Kansas in 1961, found that when the patient was breathing room air, he had an PaO2 of 96–104 mm Hg, which is in the normal range, but an arterial oxygen saturation (Sao2) of 60%.2 When breathing 100% oxygen, the patient’s Sao2 increased to 94%.2 This increase indicated incomplete saturation of the hemoglobin at lower PaO2. Their data generated the oxygen dissociation curve shown in the Figure,2 which displays a clear rightward shift from that of a normal patient. The pulse oximetry values for our patient during inhalation of room air and 5, 10, and 15 L/min oxygen via nonrebreathing facemask were consistent with this right-shifted oxygen-dissociation curve in the Figure.

The hemoglobin Kansas variant has reduced oxygen affinity, which leads to a right shift in the oxygen-dissociation curve. The oxygen tension at which hemoglobin is 50% saturated is defined as the P50. The P50 of hemoglobin Kansas is 70 mm Hg, whereas that of normal hemoglobin is 27 mm Hg. The right shift of the oxygen-dissociation curve in patients with hemoglobin Kansas leads to enhanced oxygen delivery to the tissues. In 1969, Stamatoyannopoulos et al8 demonstrated that, in patients with low-oxygen affinity hemoglobin variants, enhanced oxygen delivery to tissues reduces the erythropoietin-mediated stimulus for erythropoiesis. The reduced erythropoietic drive results in a slight decrease in hemoglobin levels in hemoglobin Kansas patients. However, none of the previously reported patients with hemoglobin Kansas have showed any signs or symptoms of anemia.1,7,9

Pulse oximetry has limitations in patients with hemoglobinopathies. Pulse oximetry is used as a surrogate for arterial measurements of Pao2 and is accurate for patients with normal oxygen-hemoglobin dissociation curves. However, patients with hemoglobinopathies can have a significant right or left shift of their oxygen-hemoglobin dissociation curves that alters their P50 and leads to inaccurate Pao2 pulse oximetry measurements.10–12 Inaccurate pulse oximetry readings in patients with hemoglobinopathies can be due to abnormal absorption spectra, an unstable hemoglobin molecule, production of methemoglobin or carboxyhemoglobin, or altered oxygen affinity. Therefore, correlating the pulse oximetry value with blood gas analysis should be considered when feasible to accurately assess oxygenation status by pulse oximetry in patients with variant hemoglobins.

Patients with hemoglobin Kansas have greater amounts of deoxygenated hemoglobin compared to oxygenated hemoglobin. However, the high levels of deoxygenated hemoglobin in hemoglobin Kansas patients produce cyanosis that requires no treatment.2 The case presented here suggests that a variant hemoglobin should also be considered in the differential diagnosis of cyanosis which commonly includes pulmonary, cardiac, and vascular diseases. However, other potential causes include the formation of methemoglobin as a result of medications such as benzocaine, nitrate, or dapsone; enzymatic deficiency such as cytochrome b5 reductase; sulfhemoglobin produced from hydrogen sulfite poisoning or sumatriptan overdose13; and variant hemoglobins.

A review of the literature revealed no previous reports of patients with hemoglobin Kansas undergoing anesthesia. In addition, we found no reports of the response to physiological and surgical stress in patients with hemoglobin Kansas. Complications for patients with hemoglobinopathies frequently result from the instability of the hemoglobin molecule. Hemoglobinopathies are a diverse group of disorders and many are rare. The Globin Gene Server (Penn State University, State College, PA), a database for human hemoglobin variants and thalassemias, is a useful resource to understand the “pathology, hematology, electrophoretic mobility, stability, ethnic occurrence, structural and functional studies”1 for each variant listed and can be accessed at http://globin.cse.psu.edu.1

Most reported hemoglobinopathy data pertain to sickle cell disease and thalassemias. We did find a few case reports of anesthetic management in patients with other rare hemoglobinopathies. Gottschalk and Silverberg10 described the anesthetic management of a patient with the unstable hemoglobin variant hemoglobin Koln, which causes hemolysis and produces methemoglobinemia. Hemoglobin Koln differs from hemoglobin Kansas in that it has an increased oxygen affinity and results in a falsely decreased Spo2. Cirenei et al14 described a 15-year-old boy with 2 known hemoglobin pathologies: alpha thalassemia and hemoglobin Bibba. When the patient had a higher baseline hemoglobin, the pulse oximetry reading was unexpectedly low, and when his hemoglobin was low, pulse oximetry readings were normal. The authors postulated that these changes in pulse oximetry occurred because hemolysis reduced the amount of unstable hemoglobin.14 These cases illustrate the variety of clinical manifestations and findings of hemoglobinopathies.

Preoperatively, it is important to understand the pathophysiology of the patient’s hemoglobinopathy, his/her current clinical status, and whether any end-organ dysfunction has occurred. Intraoperatively, blood gas analysis should be considered to assess oxygenation, because the poor correlation between Spo2 and Sao2 makes pulse oximetry unreliable. Coordination of care through discussions among the surgeon, hematologist, and anesthesiologist during the perioperative period provides the greatest opportunity to ensure the best surgical outcome for a patient with a hemoglobinopathy.

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ACKNOWLEDGMENTS

The author thanks Allan Gottschalk, MD, PhD (Professor, Department of Anesthesiology and Critical Care, Johns Hopkins University, Baltimore, Maryland) and Robert Brown, MD (Professor Department of Anesthesiology and Critical Care, Johns Hopkins University, Baltimore, Maryland) for technical editing of this manuscript.

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DISCLOSURES

Name: Yael S. Varnado-Rhodes, MD.

Contribution: This author helped review the literature and write the manuscript.

This manuscript was handled by: BobbieJean Sweitzer, MD, FACP.

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REFERENCES

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