Hematology #6 (PV, DIC, ITP, HUS, TTP, PNH) Flashcards
What is polycythemia vera?
What mutation is this caused by?
Bone marrow overproduction of all 3 myeloid stem cell lines (high RBC’s, WBC’s, and platelets)
JAK2 mutation
Symptoms and what are they due to?
-Due to increased RBC mass (hyperviscosity and thrombosis)
-Headache, dizziness, tinnitus, pruritus after hot shower, hepatosplenomegaly, facial plethora (flushing), engorged retinal veins
What are the major criteria and what are the minor criteria to diagnose PV?
Major: increased RBC mass (increased Hgb, Increased Hct), Bone Marrow biopsy showing hypercellularity, JAK2 mutation presence
Minor: decreased serum erythropoietin, Normal O2 Sat, Increased leukocyte alkaline phosphatase.
Treatment for polycythemia Vera
-Low Risk (<60 and no thrombosis: Phlebotomy until hct <45%. Low dose Aspirin.
-High Risk: All the above + Hydroxyurea.
–Ruxolitinib (JAK2 inhibitor)
-Avoid iron supplementations.
What is paroxysmal nocturnal hemoglobinuria?
RBC’s become deficient in GPI anchor surface proteins
Symptoms of PNH
-Triad of hemolytic anemia + Pancytopenia + Unexplained thrombosis in atypical veins
-Dark, cola-colored urine during night or early morning
-Thrombosis in unusual veins (hepatic, abdominal, subdermal veins)
-Hypercoagulability despite pancytopenia is HALLMARK
What’s the best test to look for PNH
-Flow cytometry test: CD55/CD59 deficient RBC’s
Treatment for PNH
-Complement inhibitors: Eculizumab
-Folic acid supplementation
-Stem Cell Transplant only cure
Thrombotic Thrombocytopenia Purpura (TTP) is due to ________
Explain what this normally does and what happens as a result.
ADAMTS13 deficiency
It normally cleaves VWF. This leads to large VWF-multimers that cause small vessel thrombosis
What can TTP can caused from (a specific autoimmune disease)
SLE
Symptoms of TTP (Pentad)
-Thrombocytopenia: Mucocutaneous bleeding
-Microangiopathic hemolytic Anemia: Splenomegaly, Anemia, Jaundice, Schistocytes on smear
-Neuro Sx: Confusion, CVA, Visual changes, AMS
-Fever
-Kidney failure or uremia
What is unique about what is seen on labs with TTP (and HUS)
-Thrombocytopenia with normal coagulation studies (Normal PT and PTT)
-Hemolysis: Schistocytes (helmet cells) or bite cells on smear
-Decreased ADAMTS13
Treatment for TTP
-Plasmapheresis (initial TOC)
-Immunosuppression: Glucocorticoids and/or Rituximab if no response to Plasmapheresis
On the other hand, Hemolytic Uremic Syndrome (HUS), is
Thrombotic microangiopathy due to platelet activation by exotoxins
Symptoms of HUS and how does this differ from TTP
-Thrombocytopenia, hemolytic anemia, renal dysfunction
NO FEVER or NEURO SYMPTOMS (seen in TTP only)
Who is HUS normally seen in?
Explain this pathophysiology
Children with recent history of gastroenteritis
Diarrhea prodrome. Shigella toxin in E-Coli damages vascular endothelium, activating platelets –> micro thrombi formation, damaging kidneys –> uremia
Labs for HUS (similar to TTP) with one different one
-Thrombocytopenia with normal coagulation studies (normal PT and PTT)
-Hemolysis: Schistocytes, helmet cells, bite cells
-Increased BUN and Cr
Treatment for HUS
-Supportive: initially
-Plasmapheresis if severe or neuro symptoms
-ABX and anti-motility agents avoided = may worsen condition
What is disseminated intravascular coagulation (DIC)
Pathological activation of the coagulation system
Explain what happens in DIC
-Uncontrolled fibrin production leads to widespread micro thrombi which consumes coagulation proteins and platelets. This leads to severe thrombocytopenia –> diffuse bleeding
Etiologies of DIC
-Infections: Gram negative sepsis MC
-Malignancies
-Obstetric: pre-eclampsia
-Burns, trauma, liver disease, AA, ARDS
Symptoms of DIC
-Bleeding: oozing from venipuncture sites, catheters, drains
-Thrombosis: gangrene or multi-organ failure
How do you diagnose DIC?
-Decreased fibrinogen (from consumption)
-Increased PT, PTT, and INR
-Thrombocytopenia
-Increased D-Dimer (Increased fibrinolysis)
-Schistocytes, Fragmented RBC’s on smear
What is immune thrombocytopenic purpura (ITP)?
Immune-mediated isolate thrombocytopenia (low platelet count)
Explain ITP and what happens in it
-Autoantibodies against platelets, leading to splenic destruction of platelets.
ITP is MC after ____________ and has symptoms such as
-Viral infection
Often asymptomatic, but mucocutaneous bleeding.
How do you diagnose ITP?
-Isolated thrombocytopenia with normal coagulation studies (PT, PTT, INR)
-Peripheral smear normal
What is seen on bone marrow biopsy in ITP?
megakaryocytes (large sized platelets)
Treatment for mild bleeding + platelets < 30,000 in adults
-Glucocorticoids (first line)
-IVIG (second line)
-Refractory: Rituximab or Splenectomy
If severe bleeding and platelets <30,000
-Platelet transfusion + IVIG + high dose glucocorticoids
In children, give ______ first if need a rapid rise in platelets.
If not a rapid rise in platelets needed, give _____
IVIG
Glucocorticoids
