Disease/Medical Condition GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY Date of Publication: October 14, 2020 (also known as “G6PD deficiency” and “erythrocyte glucose-6-phosphate dehydrogenase deficiency”; includes “favism”) Note: For more detail on the general manifestations of anemia, and those of hemolytic anemia in particular, please refer to the Anemia Fact Sheet. Is the initiation of non-invasive dental hygiene procedures* contra-indicated? No Is medical consult advised? ....................................... Yes, if G6PD deficiency is newly suspected.1 Yes, if a patient/client with known G6PD deficiency has been recently exposed to a trigger that could potentially trigger acute hemolytic anemia (AHA). Yes, if an episode of acute hemolytic anemia is suspected. This should be considered a medical emergency with immediate referral to an appropriate facility for management. Yes, if the patient/client has chronic hemolytic anemia, in which case liaison with the patient/client’s hematologist (blood specialist) or experienced internist, paediatrician, or family physician is advisable regarding the severity and management of the patient/client’s disorder before undertaking dental hygiene treatment for the first time. Is the initiation of invasive dental hygiene procedures contra-indicated?** Yes. This metabolic condition entails blood disorders (hemolytic anemia2 and methemoglobinemia) that may affect appropriateness or safety, and scaling and root planing, including curetting surrounding tissue, are contraindicated until the patient/client is medically cleared (as per Ontario Regulation 510/07 pursuant to the Dental Hygiene Act, 1991). Another potential contraindication is hypersplenism, which can cause thrombocytopenia (i.e., low platelet count, and hence increased risk of bleeding) and/or neutropenia (i.e., low neutrophil white blood cell count, and hence compromised immunity and increased risk of infection). Is medical consult advised?........................................ See above. Is medical clearance required? ................................... Yes, if G6PD deficiency and/or hemolytic anemia have been diagnosed or are suspected. (Note: Most patients/clients with G6PD deficiency, in the absence of a trigger, are merely at elevated risk of hemolytic anemia rather than actually having it or exhibiting clinically relevant signs/symptoms. – Yes, if significant thrombocytopenia exists or is suspected. – Yes, if significant neutropenia exists or is suspected . Is antibiotic prophylaxis required? .............................. No, in most cases. Potentially, if significant neutropenia exists.3 Is postponing treatment advised? ................................ Yes, pending medical clearance (and potential preventive measures or treatment for hemolytic anemia, as indicated). – Yes, if patient/client has recently been exposed to a trigger for hemolytic anemia, including certain drugs, infections (including uncontrolled oral infections), and metabolic conditions, as well as fava beans. Yes, if an episode of acute hemolytic anemia is suspected. Yes, if chronic hemolytic anemia is suspected to be severe and the patient/client has attendant signs/symptoms. Patients/ clients who are short of breath and in whom hemoglobin (Hb) levels are < 110 g/L [also expressed as 11.0 g/dL], have an abnormal heart rate, or have an oxygen saturation < 91% (as determined by pulse oximetry) are considered medically unstable, and routine dental/dental hygiene treatment should be deferred until health status improves. 1 Diagnosis is confirmed by measuring levels of the G6PD enzyme. 2 While most patients/clients with G6PD deficiency do not exhibit significant hemolysis of red blood cells in the absence of a trigger, a minority experience ongoing, chronic hemolytic anemia even in the absence of an oxidative trigger. 3 Because certain antibiotics can trigger acute hemolytic anemia in patients/clients with G6PD deficiency, careful selection of antibiotic prophylaxis is warranted. cont’d on next page... Disease/Medical Condition GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY (also known as “G6PD deficiency” and “erythrocyte glucose-6-phosphate dehydrogenase deficiency”; includes “favism”) Oral management implications The dental hygienist should be aware that certain medications (including some antibiotics and analgesics) can precipitate an acute hemolytic anemia episode in some patients/clients with G6PD deficiency.4 These include sulfa drugs (e.g., sulfacetamide, sulfadiazine, sulfamethoxazole, sulfanilamide, sulfapyridine, and dapsone); certain other antibiotics (such as quinolones [e.g., ciprofloxacin, moxifloxacin, nalidixic acid, and norfloxacin], some anti-tuberculosis drugs [e.g., isoniazid and streptomycin], as well as nitrofurantoin, cotrimoxazole, and furazolidone)5; certain analgesics (including acetylsalicylic acid [i.e., ASA, particularly in high doses] and phenazopyridine [a urinary analgesic]); certain antimalarial drugs (e.g., chloroquine, pentaquine, primaquine, and quinine); certain anti-arrhythmic agents (e.g., quinidine); certain chemotherapy drugs (e.g., doxorubicin); certain antihelminthic6 agents (e.g., niridazole); certain chelating agents (e.g., dimercaprol, which is used to treat acute poisoning by arsenic, mercury, gold, and lead); rasburicase (used to lower uric acid levels, particularly in persons undergoing treatment for leukemia, lymphoma, and certain tumours); certain anti-diabetes agents (particularly the first-generation sulfonylurea chlorpropamide); methylene blue (used to treat methemoglobinemia, and also a component of some urinary tract products); toluidine blue (a dye which has been used in vivo to identify dysplasia and carcinoma of the oral cavity); and ascorbic acid (vitamin C). In addition, camphor (a wood oil commonly used in creams, lotions, and ointments) can be a trigger. The degree of susceptibility varies between persons, with persons with lower degrees of residual G6PD activity being at higher risk and having more limitations with respect to “probably safe” drugs. Acetaminophen use within recommended therapeutic dosages is generally considered safe for most persons with G6PD deficiency (i.e., those with Class II deficiency or higher, without nonspherocytic hemolytic anemia).7 Similarly, many non- steroidal anti-inflammatory drugs within recommended dosages are probably safe for most persons with G6PD deficiency.8 Local anaesthetic agents (e.g., prilocaine, lidocaine, and articaine), topical benzocaine, and silver nitrate have been reported to induce methemoglobinemia9 in G6PD deficient persons. However, as with analgesics and antibiotics commonly used in the dental setting, there is considerable debate regarding which anaesthetic drugs should be generally or selectively avoided. While inhalation sedation is usually safe, general anaesthesia should generally be given in a hospital environment. The dental hygienist should be aware that infection — including uncontrolled oral infection — is a trigger for acute hemolytic anemia in patients/clients with G6PD deficiency.10 Dental infections should be avoided, and if they occur, be managed quickly and effectively. 4 Medical references are inconsistent regarding “unsafe” versus “probably safe” drugs in persons with G6PD deficiency. This is a general, non- exhaustive list and may not apply to all G6PD-deficient individuals. According to some authorities, some medications previously thought to be unsafe are probably safe in usual therapeutic doses. Individual characteristics (e.g., degree of G6PD deficiency, dose, presence of infection, etc.) will influence actual safety or injury. 5 Penicillin and amoxicillin have also been rarely implicated in hemolysis in persons with G6PD-deficiency. 6 anti-helminthic agent = anti-parasitic drug for worms 7 The World Health Organization’s classes of G6PD deficiency are: I (congenital nonspherocytic hemolytic anemia and chronic hemolysis without exposure to oxidative stressors; rare, and tends to be in white males of Northern European background); II (severe deficiency, with 1-10% residual activity and intermittent oxidative stress-induced hemolysis; prototype is G6PD-Mediterranean); III (mild deficiency, with 10-60% residual activity and intermittent oxidative stress-induced hemolysis; most common type); IV (60-150% -- normal activity, with no clinical sequelae); and V (> 150% -- increased activity, with no clinical sequelae). 8 Case reports of NSAID-linked hemolytic anemia in G6PD-deficient persons exist in the medical literature. 9 Methemoglobinemia (congenital or acquired) occurs when red blood cells (RBCs) contain methemoglobin at levels higher than 1%. Methemoglobin results from the presence of iron in RBCs in the ferric rather than the usual ferrous form. If the activity of G6PD is low, ferrous to ferric conversion occurs when RBCs are exposed to oxidizing triggers, resulting in methemoglobinemia (oxidized hemoglobin molecules), which impedes availability of oxygen to tissues. 10 According to some authorities, infection is probably the most common trigger inciting hemolysis in children who are G6PD deficient. Microbial triggers include E. coli, Rickettsia, cytomegalovirus, hepatitis A, hepatitis B, typhoid, beta-hemolytic streptococci, pneumonia, and those related to deep carious lesions and maxillofacial infections. cont’d on next page... 2 Disease/Medical Condition GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY (also known as “G6PD deficiency” and “erythrocyte glucose-6-phosphate dehydrogenase deficiency”;