Presentations

Abstract

Introduction: Hemolytic anemia has a broad differential with common causes including infections and autoimmune causes. Diagnosis can present a challenge since it can be seen as a subsequent pathology from a larger unifying diagnosis or as the cause of many of the symptoms patients might present with. Paroxysmal nocturnal hemoglobinuria(PNH) is a rare disease that affects approximately 16 people per million worldwide. If left untreated and undiagnosed, it can lead to significant morbidity and mortality.

Case Information: 34 year old male with limited to no contributory past medical history with occupational exposure to non-ionizing radiation and frequent outdoor exposure and recent unknown origin dog bite approximately a week ago. Coming in with a chief complaint of intermittent episodic non-exertional chest pain, dizziness, pre-snycope, and darkened urine. He states this has been ongoing and most recently has worsening. Laboratory and clinical workup was revealing for Anemia 9.8 g/dl, Troponins of 414 ng/L, WBC 5.1 K/ul , LDH 268 U/L, Haptoglobin <10 mg/dl, ESR 77, CRP 6.4, negative direct and indirect coombs testing, without evidence of schistocytes or other abnormalities on blood smear, Initial CT head non-revealing, Coronary CT without coronary calcifications with concerns for possible myocarditis confirmed on cardiac MRI, Echocardiogram and EKG without acute concerns. Lumbar puncture with CSF was non-revealing on both fluid analysis and microbiological analysis. Serological microbial analysis was non-revealing. An autoimmune workup only revealed mildly elevated anti-cardiolipin that did not meet diagnostic criteria. Infectious disease started on empiric complete 10 day course of doxycycline due to concerns of tick-bite-induced infection and started on tx regimen for rabies given dog bite. Hematology and oncology started on intravenous immunoglobulin and steroids for empiric treatment of autoimmune hemolytic anemia. Cardiology started on colchicine for 60 days without further intervention needed. Patient remained stable without chest pain during visit. Patient experienced dizziness and anterograde amnesia in which CT-Angiography, CT head and MRI revealed new onset strokes not previously seen. Eventually due to clinical suspicion,Glycosylphosphatidylinostiol(GPI) CD55/59 testing was performed and returned with 3.7% partial and 15.14% complete deficiency of surface protein consistent with diagnosis of paroxysmal nocturnal hemogloburia due to rarity of this presentation the test was confirmed on repeat. Patient was started on eliquis due to increase risk of thrombosis and is to be evaluated for outpatient evaluation to start on anti-c5 biologic such as ravulizumab after proper vaccination against streptococcal and meningococcal infections.

Discussion/Clinical Findings: PNH is an X-linked acquired genetic mutation of hematopoietic stem cells involved in the production of glycosylphosphatidylinositol (GPI) surface protein which connects CD55 and CD59 for cellular modulation of complement activation(1). When not seen on surface, this leads to paroxysmal stress-induced complement-mediated hemolysis. Symptoms include thrombosis, shortness of breath, fatigue(1). Laboratory findings are characteristic of hemolytic anemia without findings of auto-antibodies. Diagnosis is confirmed with flow cytometry for GPI associated CD55 and 59. Treatment revolves around anti-complement biologic therapies to avoid hemolysis with ultimate goal to prevent hemolysis and need for transfusion(1). Without treatment, life span is significantly shortened to approximately 1 to 2 decades after diagnosis and development of the disease(1). With treatment, life expectance approaches that of the population. The most frequent cause of mortality and morbidity in those with PNH is due to the hypercoagulable state of their(1). This case corroborates with the typical findings seen in PNH, however myocarditis is not typically reported nor exact source cannot be elucidated from clinical and laboratory diagnosis. Other studies indicate the theoretical that severe anemia can lead to cardiac cellular dysfunction(2). Given his likely prolonged anemia, this might be considered complication of PNH and will need to monitor for resolution and recurrence with treatment of underlying disease before more definitive answer can be given.

Conclusion: Hemolytic anemia can present with elusive multiorgan system involvement. A rare but serious cause of this is PNH, clinical suspicion should remain high if infectious and other autoimmune causes have been ruled out as this can significantly increase lifespan. This is important as those who typically present are in their 3rd and 4th decade of life(1).