Hematology #6 (PV, DIC, ITP, HUS, TTP, PNH)

Question 1

What is polycythemia vera?

What mutation is this caused by?

Answer 1

Bone marrow overproduction of all 3 myeloid stem cell lines (high RBC’s, WBC’s, and platelets)

JAK2 mutation

Question 2

Symptoms and what are they due to?

Answer 2

-Due to increased RBC mass (hyperviscosity and thrombosis)

-Headache, dizziness, tinnitus, pruritus after hot shower, hepatosplenomegaly, facial plethora (flushing), engorged retinal veins

Question 3

What are the major criteria and what are the minor criteria to diagnose PV?

Answer 3

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.

Question 4

Treatment for polycythemia Vera

Answer 4

-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.

Question 5

What is paroxysmal nocturnal hemoglobinuria?

Answer 5

RBC’s become deficient in GPI anchor surface proteins

Question 6

Symptoms of PNH

Answer 6

-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

Question 7

What’s the best test to look for PNH

Answer 7

-Flow cytometry test: CD55/CD59 deficient RBC’s

Question 8

Treatment for PNH

Answer 8

-Complement inhibitors: Eculizumab
-Folic acid supplementation
-Stem Cell Transplant only cure

Question 9

Thrombotic Thrombocytopenia Purpura (TTP) is due to ________

Explain what this normally does and what happens as a result.

Answer 9

ADAMTS13 deficiency

It normally cleaves VWF. This leads to large VWF-multimers that cause small vessel thrombosis

Question 10

What can TTP can caused from (a specific autoimmune disease)

Answer 10

SLE

Question 11

Symptoms of TTP (Pentad)

Answer 11

-Thrombocytopenia: Mucocutaneous bleeding
-Microangiopathic hemolytic Anemia: Splenomegaly, Anemia, Jaundice, Schistocytes on smear
-Neuro Sx: Confusion, CVA, Visual changes, AMS
-Fever
-Kidney failure or uremia

Question 12

What is unique about what is seen on labs with TTP (and HUS)

Answer 12

-Thrombocytopenia with normal coagulation studies (Normal PT and PTT)
-Hemolysis: Schistocytes (helmet cells) or bite cells on smear
-Decreased ADAMTS13

Question 13

Treatment for TTP

Answer 13

-Plasmapheresis (initial TOC)
-Immunosuppression: Glucocorticoids and/or Rituximab if no response to Plasmapheresis

Question 14

On the other hand, Hemolytic Uremic Syndrome (HUS), is

Answer 14

Thrombotic microangiopathy due to platelet activation by exotoxins

Question 15

Symptoms of HUS and how does this differ from TTP

Answer 15

-Thrombocytopenia, hemolytic anemia, renal dysfunction

NO FEVER or NEURO SYMPTOMS (seen in TTP only)

Question 16

Who is HUS normally seen in?

Explain this pathophysiology

Answer 16

Children with recent history of gastroenteritis

Diarrhea prodrome. Shigella toxin in E-Coli damages vascular endothelium, activating platelets –> micro thrombi formation, damaging kidneys –> uremia

Question 17

Labs for HUS (similar to TTP) with one different one

Answer 17

-Thrombocytopenia with normal coagulation studies (normal PT and PTT)
-Hemolysis: Schistocytes, helmet cells, bite cells
-Increased BUN and Cr

Question 18

Treatment for HUS

Answer 18

-Supportive: initially
-Plasmapheresis if severe or neuro symptoms
-ABX and anti-motility agents avoided = may worsen condition

Question 19

What is disseminated intravascular coagulation (DIC)

Answer 19

Pathological activation of the coagulation system

Question 20

Explain what happens in DIC

Answer 20

-Uncontrolled fibrin production leads to widespread micro thrombi which consumes coagulation proteins and platelets. This leads to severe thrombocytopenia –> diffuse bleeding

Question 21

Etiologies of DIC

Answer 21

-Infections: Gram negative sepsis MC
-Malignancies
-Obstetric: pre-eclampsia
-Burns, trauma, liver disease, AA, ARDS

Question 22

Symptoms of DIC

Answer 22

-Bleeding: oozing from venipuncture sites, catheters, drains
-Thrombosis: gangrene or multi-organ failure

Question 23

How do you diagnose DIC?

Answer 23

-Decreased fibrinogen (from consumption)
-Increased PT, PTT, and INR
-Thrombocytopenia
-Increased D-Dimer (Increased fibrinolysis)
-Schistocytes, Fragmented RBC’s on smear

Question 24

What is immune thrombocytopenic purpura (ITP)?

Answer 24

Immune-mediated isolate thrombocytopenia (low platelet count)

Question 25

Explain ITP and what happens in it

Answer 25

-Autoantibodies against platelets, leading to splenic destruction of platelets.

Question 26

ITP is MC after ____________ and has symptoms such as

Answer 26

-Viral infection

Often asymptomatic, but mucocutaneous bleeding.

Question 27

How do you diagnose ITP?

Answer 27

-Isolated thrombocytopenia with normal coagulation studies (PT, PTT, INR)
-Peripheral smear normal

Question 28

What is seen on bone marrow biopsy in ITP?

Answer 28

megakaryocytes (large sized platelets)

Question 29

Treatment for mild bleeding + platelets < 30,000 in adults

Answer 29

-Glucocorticoids (first line)
-IVIG (second line)
-Refractory: Rituximab or Splenectomy

Question 30

If severe bleeding and platelets <30,000

Answer 30

-Platelet transfusion + IVIG + high dose glucocorticoids

Question 31

In children, give ______ first if need a rapid rise in platelets.

If not a rapid rise in platelets needed, give _____

Answer 31

IVIG

Glucocorticoids