• Normally, RBCs remain soluble and flexible in the blood when passing through the circulation at varying degrees of oxygen saturationSickle-Cell-Anemia-Occlusion-1Mechanism
  • In Sickle cell anemia: substitution of VALINE for GLUTAMIC ACID in position 6 of the Beta-chain => This substitution results in an alteration of the quaternary structure of the hemoglobin molecule
  • When de-oxygenated, the mutated RBCs will form long polymers & cross linking; thus becoming rigid and insoluble
  • MECHANISM: The loss of the hydrophilic AA for a hydrophobic AA will allow it to interact with hydrophobic AA helices on another B chain and form aggregates
  • These sickled cells form polymers with themselves; they lose flexibility and a collection of rigid sickle cells will cause occlusion in the micro circulation
  • Upon returning to oxygenated tissue, the cells will be able to return to their discoid cell shapes
  • Repeated sickling will cause ion channel dysfunction (loss of Ca2+/K+), cellular dehydration (will be permanently sickled and destroyed in the spleen)


  1. Deepa Manwani and Paul S. Frenette. Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies. ASH Education Book December 6, 2013 vol. 2013 no. 1 362-369
  2. Chapter 49: Disorders of Hemoglobin Structure: Sickle Cell Anemia and Related Abnormalities. Kavita Natrajan; Abdullah Kutlar. Williams Hematology, 9e
  3. Odièvre M-H, Verger E, Silva-Pinto AC, Elion J. Pathophysiological insights in sickle cell disease. The Indian Journal of Medical Research. 2011;134(4):532-537.

Signs of intravascular hemolysis include:

  1. Elevated lactate dehydrogenase (marker of tissue damage)
  2. Reduction in haptoglobin (binds free hemoglobin [Hb])
  3. UNnconjugated hyperbilirubinemia (byproduct of hemolysis)

*Be certain to check for increased reticulocytes ( bone marrow compensatory response) and blood smear (i.e Spherocytes, Schistocytes, Sickle cells)


  1. W. Barcellini and B. Fattizzo, “Clinical Applications of Hemolytic Markers in the Differential Diagnosis and Management of Hemolytic Anemia,” Disease Markers, vol. 2015, Article ID 635670, 7 pages, 2015. doi:10.1155/2015/635670
  2. Kato GJ, McGowan V, Machado RF, et al. Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease. Blood. 2006;107(6):2279-2285. doi:10.1182/blood-2005-06-2373.

When you start a patient on Warfarin (i.e after a PE); there will be an overlap of administration of Warfarin and LMWH/ UFH for typically 5 days with a goal INR of 2-3. This is referred to as “Bridging“.

WHY? Warfarin introduces a temporary hypercoagulable stage during the first 36 hours. Protein C and Protein S (anti-coagulation factors) are vitamin K-dependent plasma proteins. Levels of these anti-coagulation factors drop faster than the pro-coagulation factors (10,9,7,2) we attempt to block with Warfarin. Therefore, bridging is used to counteract this transient pro-clotting state.


  1. Esmon CT, Vigano-D’Angelo S, D’Angelo A, Comp PC. Anticoagulation proteins C and S. Adv Exp Med Biol. 1987;214:47-54.
  2. Protein C / Protein S anticoagulant pathway. Anticoagulant pathway. Jeremy Parsons, M.D. (c) 2002-2016, PathologyOutlines.com, Inc.

Hypercalcemia affects up to a third of cancer patients and malignant hypercalcemia is the most common oncological emergency leading to hospitalization.

Most likely to occur in: breast cancer, multiple myeloma and lung cancer. However, it can also be found in other malignancies, including: gynecologic, renal and head & neck cancers

CAUSE: Increased osteoclastic bone resorption.

  • Solid tumours can produce parathyroid hormone–related protein (PTHrP), increasing calcium levels in the blood by activating parathyroid hormone receptors in tissue, which results in osteoclastic bone resorption; it also increases renal tubular resorption of calcium.
Source: Journal of the American Society of Nephrology


  1. Bower M, Cox S. Endocrine and metabolic complications of advanced cancer. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford textbook of palliative medicine. 3rd ed. New York, NY: Oxford University Press; 2004. pp. 688–90.
  2. Lumachi F, Brunello A, Roma A, Basso U. Cancer-induced hypercalcemia. Anticancer Res. 2009;29(5):1551–5.
  3. Seccareccia D. Cancer-related hypercalcemia. Canadian Family Physician. 2010;56(3):244-246.


    • FNHTR [Febrile non-hemolytic transfusion reaction] (5% with platelets, <1% with RBCs), allo-immunization to red cell antigen


    • TACO [Transfusion associated circulatory overload] 
    • TRALI [Transfusion-related acute lung injury] 
    • Acute hemolytic transfusion reaction
    • Anaphylactic reaction 
    • Hyperkalemia & Hypocalcemia 


    • Hepatitis B (1/150,000), Hepatitis C (1/2-3 million), HIV (1/7.8 million)


  1. Chapter 12. Hematopathology. Pathology: The Big Picture


often no cause (cause be due to URTI, SLE, HIV, HCV)
  • Acute: children (2-6 y.o) => abrupt hemorrhagic complication following viral illness 
  • Chronic: insidious onset (no disease relation), most often in adults 20-40 (3:1 Female:Male)
IgG antibodies formed against the patient’s platelets
Clinical Presentation
  • minor bleeding/ easy bruising 
  • petechiae, hematuria, hematemesis or melena
  • General no splenomegaly 
  • Look for increase megakaryocytes due to increase bone marrow production 
  • thrombcytopenia
*diagnosis of exclusion 

  • Most children will have spontaneous resolution of ITP 
  • Treatment typically reserved for people with symptomatic bleeding 
  • If >20,000 platelets, typically asymptomatic 
  • 1) IVIG (wait 12-24hr and check platelets 2) corticosteroids 3) splenectomy 


Due to lose of ADAMTS13 cleaving vWF => causes formation of platelet microthrombi that occlude small blood vessels, shear RBCS (schistocytes) and causes end organ damage. 
CAUSES: unknown, can be due to infections, bacteria toxins, drug related, autoimmune, or idiopathic 
BLOOD SMEAR: schistocytes
  • Also known as “helmet cells”
  • fragmented RBC’s due to MAHA (formation of platelet-fibrin mesh due to increased activation of coagulation)
1) Neurological symptoms (delirium, seizure, stroke) 
2) Renal dysfunction (increase Cr)
3) Fever
4) Thrombocytopenia
5) Microangiopathic hemolytic anemia


  • DO NOT give platelets (contraindicated); it may worsen the condition