Flashcards in Elevated Blood Counts Deck (45):
What myeloproliferative diseases can cause neutrophilia?
What are some non-myeloproliferaitve causes of neutrophilia?
What are some causes of increased platelets?
-myeloproliferative neoplasm (ET/MF/PV/CML-all of them)
What are myeloproliferative neoplasms?
hematopoietic neoplasms in which a clone of cells is mutated early in the differentiation of blood cells, such that these cells can differentiate fully into red cells, platelets and neutrophils, BUT no longer are well controlled in number, thus producing too many of one or more cell lines with fairly normal appearing and fairly normal functioning cells.
Central to MPNs is what?
understanding of the EPO receptor that is a JAK/STAT system which uses JAK-2 kinase
Mutated JAK2 kinase leads to what?
continuously active EPO pathway with or without EPO presence
A JAK2 mutation is most common in which MPN?
ET and Primary MF may have JAK2 mutation in up to 60% of cases and if they don't, they have a mutation in MPL (TPO receptor) or CALR (calreticulin)
What happens in PV?
too many red cells which leads to increased plasma volume, dilation of the veins, and other symptoms
What are the most common physical findings of PV?
From most to least:
-engorged retinal vessels
-hypertension (systolic high more often)
What are the most common symptoms of PV?
-diaphoresis (excess sweating)
PV hurts 2 people, dogs, and daughters
What are common complications/causes of death in PV patients?
-thrombosis/embolism (very common)
-progression to AML
-progression to myelofibrosis (become pancytopenic)
What is the median survival time from start of treatment (phlebotomy) in PV patients?
What is commonly seen in a PV blood smear?
-too many platelets
-hypochromic microcytic cells due to iron deficiency (GI blood loss is common)
What does the bone marrow look like in PV patients?
-very hyper cellular
-clusters of megakaryocyes
What are some risk factors for thrombosis in PV patients?
How is PV diagnosed?
1) Hemoglobin greater than 18.5+ in men, 16.5 in women
2) Presence of JAK2617V mutation or JAK2 exon 12 mutation
3) EPO below normal range
How is PV treated?
Target HCT 45% (prevents thrombosis well)
100 mg/d significantly lowers combined risk of CV death, non-fatal myocardial infarction, non-fatal stroke, major thromboembolism (hazard ratio 0.4). Relative risk increase in major bleeding with ASA 1.6.
Very effective in reducing thrombosis (1.6% vascular events/yr vs 10.7%)
Target HCT of 45 with WBC >3000, supplement with phlebotomies if needed
No clear increase in leukemic transformation
3 million units/d until response and then lower
Peg-interferon 0.5 mcg/kg weekly increased to 1.0 if no response in 12 weeks
Blood 112:8 3065—35/40 CR at I year
Can control platelets and HCT in Majority of patients and reduce spleen size and alleviate pruritus
May work when Hydrea fails
Busulfan reasonable in elderly patients
5) JAK2 inhibitors
Symptoms of ET:
-erythromelalgia (severe burning pain of the forefoot)
What is commonly seen in the bone marrow (and sometimes the blood smear) in ET?
large numbers of megakaryocytes
How is ET diagnosed?
Platelets elevated (450 K/ul) without red cell elevation or iron deficiency and positive JAK2 mutation. IF JAK2 not positive, look in bone marrow for MPL or calreticulin mutation
If platelets get above 1.5 million, what can happen?
they may acquire vmF diseases with loss of large vFM multimers resulting in bleeding (purpura)
For major bleeding events in ET (can happen), what is the treatment?
- Correct thrombocytosis
- Withdraw aspirin
What is the treatment for ET?
need to reduce platelets:
-Hydroxyurea (affects all cell lines-leads to pancytopenia)
-Interferon (pregnancy risk)
What does Anagredile do?
inhibits megakaryocytes= less platelets
Side effects of Anagredile?
-increased arterial thrombosis risk
only used when Hydroxyurea not working
What are the criteria for "high risk" for ET and should be treated with platelet reduction?
- 60+ y/o
- platelets above 1500K/ul
- previous thrombosis, erythromelagia
What happens in primary MF?
fibrosis in BM, hematopoiesis is crowded out and moves to spleen and liver thus producing splenomegaly
What other MPN causes splenomegaly?
What are some common findings in primary MF?
-fatigue and anemia
-thrombocytosis or -penia
MF can also arise from other things and is called 'secondary' MF. What neoplastic conditions can lead to secondary MF?
-acute megakaryoblastic leukemia
-myelodysplasia with fibrosis
What non-neoplastic conditions can lead to secondary MF?
great post high
What is the key findings in a peripheral smear of a primary MF patient?
-tear drop cell (dacrocyte) non-specific
How is primary MF diagnosed?
Patient comes in with constitutional symptoms, spleen is enlarged, check bone marrow and check for JAK2, calreticulin, and Mpl mutations
How is primary MF treated?
Allo SCT or JAk2 inhibitors
What MPN is Philadelphia chromosome positive?
CML t(9,22) ABL-BCR
What is CML?
condition where you have way too many white cells and you develop early white cells in the peripheral blood. Blood smear shows early neutrophils, particularly myelocytes
How would a CML patient present?
with elevated neutrophil count, usually not ill. Often a palpable spleen
How is CML diagnosed?
Diagnosis made by FISH or pcr for bcr-abl fusion transcripts,
Or by bone marrow with symptoms present and cytogenetics for 9:22 translocation
What is the prognosis for CML?
Used to Be: Prognosis was 3-4 years survival with 25% converting to AML each year; allogeneic transplant was only cure and treatment of choice for those able.
Now we have tyrosine kinase inhibitors (Imatinib)
How is CML treated? Goals of treatment?
Initial therapy is with Imatinib
Goal is complete cytogenetic response with no evidence of Philadelphia chromosome, or major molecular response with a 3 log reduction of bcr-abl transcripts by pcr technique
What is hypereosinophilia caused by?
How is hypereosinophilic syndrome defined?
greater than 1500 level of eosinophils for over 6 months and start to see heart and lung damage
What are some possible causes of Hypereosinophilic syndrome?
-chronic eosinophilic leukemia
-hematopoietic neoplasms accompanied by eosinophilia (T cell clonal disorders, AML, MPN-eos, MDN-eos)
What are some complications of hypereosionphilic patients?