Today, we discussed the case of a previously healthy young man who was found to have a DVT as an outpatient and prior to initiating anti-coagulation, was noted to have significant microcytic anemia. Ultimately, his work-up revealed a metastatic malignant process, likely GI primary.
We generated a short starter list (not exhaustive) for entities whose illness script includes anemia (w/o obvious signs of blood loss) and DVT. A few pathophysiologic explanations follow the syndromes. Feel free to add/comment with more!
Anemia + DVT ddx
-Sideroblastic anemia, thalassemia**
-Myeloproliferative neoplasms, PNH
*From the Annals of Hematology: while concomitant thrombocytosis tends to be involved in iron-related thrombosis, iron-deficiency on its own may contribute to a hypercoagulable state through anemic hypoxia or by affecting blood flow patterns within the vessels because of reduced deformability and increased viscosity of microcytic red blood cells
**Patients with thalassemia (mild, intermediate, or major clinical phenotype) have chronically activated platelets, enhanced platelet aggregation, and have higher levels of pro-coagulant microparticles of RBC, leukocytes, and endothelial membrane compared to controls. Per the Mediterranean Journal of Hematology and ID which has many more touches with thalassemia than us, “the presence of other peripheral blood elements in [patients with thalassemia] such as E-selectin (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), von Willebrand factor (VWF) and vascular cell adhesion molecule-1 (VCAM-1) indicates that endothelial injury or activation may be an aspect of the disease, aiding in the recruitment of white blood cells and RBCS, promoting thrombosis.”
***In patients who have undergone splenectomy (see blood smear below with H-J bodies 🙂, there are more exposed pro-coagulant phospholipids on altered membranes of the abnormal erythrocytes–and these are no longer removed by splenic macrophages. Studies suggest that in patients who are post-splenectomy, there is a higher number of negatively charged RBCs and increased thrombin generation!
At a recent intern report, we discussed the entity of DRESS or drug reaction with eosinophilia and systemic symptoms AKA drug-induced hypersensitivity syndrome (DISH). This diagnosis is under the larger umbrella of severe cutaneous adverse reactions to drugs (SCARs).
- While adverse cutaneous reactions to drugs affect 2% to 3% of all hospitalized patients, only 2% of these are considered severe
- Spectrum of SCARs:
- Acute Generalized Exanthematous Pustulosis (AGEP)
- Drug reaction with eosinophilia and systemic symptoms (DRESS) or Drug-induced Hypersensitivity Syndrome (DISH)
- Epidermal necrolysis (Stevens-Johnson syndrome-SJS, toxic epidermal necrolysis –TEN)
There is a nice review of SCARs in NEJM from 2012: “Features of Selected Severe Cutaneous Adverse Reactions to Drugs.” A few key points and classy comparison table are below.
- Exanthematous drug eruptions, also called morbilliform or maculopapular drug rashes, occur in 1 to 5% of first-time users of most drugs (whoa!)
- Identifying and discontinuing the causative drug are the most important steps in management
- Symptomatic treatment with antipruritic agents and potent topical glucocorticoids may be helpful.
- Signs and symptoms that should alert the clinician to the possibility of a severe cutaneous reaction (SCARs): mucous-membrane involvement, temperature above 38.5°C, blisters, facial edema and erythema, and lymphadenopathy.
Despite the ambiguities among all the severe cutaneous adverse reactions to drugs (SCARs), there is actually minimal overlap in diagnoses as discussed in this article from the Journal of Rare Diseases (no joke!) looking retrospectively at 216 cases of SCARs: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517389/
- Franchini M, Targher G, Montagnana M, Lippi G. Iron and thrombosis. Annals of Hematology. 2008;87(3):167-173. doi:10.1007/s00277-007-0416-1.
- Succar J, Musallam KM, Taher AT. Thalassemia and Venous Thromboembolism. Mediterranean Journal of Hematology and Infectious Diseases. 2011;3(1):e2011025. doi:10.4084/MJHID.2011.025.
- Byrne MT, Bergman AK, Ruiz AI, Silver BJ, Maciejewski JP, Tiu RV. Postsplenectomy thromboembolic disease in congenital sideroblastic anaemia. BMJ Case Reports. 2010;2010:bcr1220092514. doi:10.1136/bcr.12.2009.2514.
- Stern RS. Features of Selected Severe Cutaneous Adverse Reactions to Drugs N Engl J Med 2012;366:2492-2501. http://www.nejm.org/doi/full/10.1056/NEJMcp1104080?rss=mostEmailed
- Bouvresse S, Valeyrie-Allanore L, Ortonne N, et al. Toxic epidermal necrolysis, DRESS, AGEP: Do overlap cases exist? Orphanet Journal of Rare Diseases. 2012;7:72. doi:10.1186/1750-1172-7-72.