Answer:

The first thing that jumps out to me is that this is a fairly young and healthy patient, they should not be anemic to 10.2. More to the point, their MCV is very low with an elevated RDW. An elevated RDW tells me there is a heterogeneous process going on - either there is not enough fuel for each cell to be big enough (Fe def.) or there is hemolysis with ongoing reticulocytosis. Going through our microcytic anemia differential, iron deficiency is ruled out by the iron studies. Anemia of chronic disease is likewise ruled out by labs but also there is no chronic disease evident to cause such an anemia. Finally, we get to the thalassemias. Some of the data does not match a pure thalassemia as they do not cause elevated RDWs.

What does the electrophoresis tell us? A normal hemoglobin molecule (Hgb A2) is made up of two alpha and two beta subunits. A normal adult has more than 90% Hgb A and a little of a normal variant (Hgb A2). A patient with Sickle Cell Anemia has no Hgb A or A2, and near 100% Hgb S. A patient with Sickle Cell Trait has some Hgb A and usually < 50% Hgb S. In these cases, occlusive crises and complications are rare. Beta-thalassemias are characterized by a mutation in the beta-globin chain either leading to a complete knock out (o) or a decrease efficacy (+) beta-chain. Beta-Thalassemia Major implies a complete absence of the beta-globin leading to no Hgb A or A2 production and nearly all Hgb F. Beta-Thalassemia Minor and Intermedia will have some beta-globin function, leading to variable Hgb A and A2 expression (anywhere from 5 to 90%).

Both Beta-Thalassemia Minor and Sickle Cell Trait are asymptomatic individually, but if they are concurrent you get a Sickle Cell Disease. This patient has a low Hgb A, a high Hgb A2, and a high Hgb S consistent with S/B+ Thalassemia. The patient’s recurrent back pain was likely related to vaso-occlusive crises.

Answer:

Fatigue and dyspnea can have a broad differential, but there is enough information above to quickly focus our attention. This patient is presenting with symptomatic anemia. From here, we note that he has a slightly elevated LDH, haptoglobin is low, and the reticulocyte index suggests the bone marrow is making an adequate amount of RBCs. So we can conclude our patient has hemolytic anemia with an adequate bone marrow response.

Hemolytic anemia itself is not an endpoint diagnosis. Why is this patient hemolyzing? While we did not give you a Coombs test, the answer lies in looking at the cell differential, physical exam, and peripheral blood slide. This patient has had an absolute lymphocytosis (>5,000 lymphocytes) on multiple CBCs, he has b-symptoms and lymphadenopathy, and he has smudge cells on his smear. While you need flow cytometry to make the final diagnosis, we have strong clinical evidence that this patient has Chronic Lymphocytic Leukemia (CLL) which is likely causing an auto-immune hemolytic anemia (AIHA).

The pathophysiology of CLL can explain how these two are connected. CLL is an unstable monoclonal expansion of malignant B-cells, which produce antibodies. The antibodies can become self-directed causing auto-immune pathology such as AIHA and ITP. CLL can also be complicated by hypogammaglobulinemia leading to recurrent infections (often pneumonia) and malignant transformation to acute leukemias (Richter Transformation).

Answer:

This is a clear case of upper GI bleed due to NSAID induced peptic ulcer disease. This patient should get an IV PPI, 2x large bore PIVs, type and screen, made NPO, and a GI consult with an EGD in the future. But this case is not about diagnosis but about interpreting data and triaging.

The first impulse clinicians often have when monitoring bleeding severity is the hemoglobin-compared-to-baseline*. In this case, the patient’s hemoglobin is right around his baseline which may provide false reassurance that this patient is stable. However, and this may be weird to hear, bleeding does not cause a decrease in your hemoglobin! If you look at the units for hemoglobin, it is grams per deciliter. This is a concentration. When you bleed, you lose whole blood and the concentration should not change. The hemoglobin decrease is a diluational effect from interstitial fluid returning into the vasculature. This process is accelerated by fluid resuscitation. Do not be falsely reassured by a normal hemoglobin in the context of a GI bleed.

The vitals for this patient paint a different picture of this patient. While the blood pressure is nothing exciting, near normal in fact, it is important to take the clinical context into account. This is a patient with significant hypertension on three medications who is now normo-to-hypotensive without any medications - that is a big change. If you were to do orthostatic vitals on this patient, they would be grossly abnormal. Additionally, this patient is “mildly tachycardic” but no 53 y/o should have a heart rate anywhere near 103 while at rest. This patient is quite ill with likely a severe upper GI bleed and should be treated as such. I would call a GI consult on admission regardless of the time of day.

Answer:

The combination of anemia, AKI and thrombocytopenia triggers concern for TTP. In these cases, the peripheral blood smear is often reduced to a binary interpretation - “there are schistocytes” or “there are no schistocytes”. However, a more subtle read can provide critical insight into this patient’s clinical picture. Looking at the slide, we see a significant amount of acanthocytes and target cells with just 1 schistocyte (see image below). This tells us that there are irregularities in the red blood cell membranes causing them to be fragile and unstable. This is often a sequela of liver disease as a result of abnormal cholesterol metabolism. Finally, there are schistocytes, but very few, just in this high powered field suggesting a low level of hemolysis which could be explained by fragile cells stressed by an external force such as an infection or medication.

The labs support some what we saw on the slide. The LDH is mildly elevated, the haptoglobin is low, the bilirubin is normal which is suggestive of hemolysis but not enough to raise the bilirubin or significantly elevate the LDH. As haptoglobin is incredibly sensitive hemolysis, decreasing rapidly in the presence of even a small amount free hemoglobin, think of it as a marker of the presence of hemolysis rather than the degree of hemolysis.

If we then look at the entire clinical picture, we have a pancytopenic patient with a history of liver transplant on immunosuppression who presented with CMV viremia. The blood slide and hemolysis labs tend to suggest a chronic process of some underlying liver disease causing fragile red blood cells that is exacerbated by an acute process causing pancytopenia. My framework for pancytopenia includes thinking about intrinsic and extrinsic bone marrow causes. Intrinsic causes include infiltrative processes such as hematologic malignancies or metastases, MDS, myeloproliferative disorders and infections such as TB or fungal infections. Extrinsic processes include bone marrow suppressive factors such as viral infections, medications, or autoimmune processes. This patient has a number of extrinsic causes for bone marrow suppression (ganciclovir, MMF, CMV viremia) that make it hard for the marrow to produce cells superimposed over an already unstable production of red blood cells. As an FYI, high tacrolimus levels can also cause a medication induced TMA.