Week 17 Blood III Flashcards
Acute Leukemia Treatment
Treatment of CNS disease secondary to ALL
- ## Intrathecal Chemotherapy
5 things to know about Acute Leukemia
- AML and ALL may occur at any age (All more common in kids and AML more common in adults)
- AML is more common than ALL
- AML and ALL are fatal without treatment (bone marrow failure leading to bleeding/infection)
- prognosis and best treatment depends on genetic profile
- 2 phases of treatment – remission induction and post remission (cure)
5 things to know about Myodysplastic Syndrome
- Disease of the older adult
- commonly presents as fatigue
- should be expected in older patients with macrocytic anemia
- patients with unexpected or severe cytopenia should be referred to a hematologist
- Active treatment is available and can improve outcomes (treatment to address the cytopenia (rhEpo), prevent or delay AML and prolong life HMA)
Neutropenia
Low Absolute Neutrophil Count (ANC)
- can be very bad
- 1< ANC <1.5 mild - minimal risk of infection
- 0.5 <ANC<1 Moderate - moderate risk of infection
- <0.5 severe - hgih risk of infection
- <0.2 very severe - very high risk of infection
- can be:
- acute and transient or
- chronic and persistent (3 months is the threshold)
Acute neutropenia
- caused by some infections, viral bacterial or protazoal
- associated with immune disorders, auto-immune diseases
- can be caused by drugs (anticonvulsants, antipsychotics etc)
- always consider if they started a new drug
Chronic neutropenia
- may be intrinsic to bone marrow (congenital - cyclic neutropenia OR Acquired - MDS)
- may be extrinsic to bone marrow (nutritional - malnutrition, B12, copper OR immune - RA, SLE, LGL )
Costovertebral Angle Tenderness
- useful in physical exam
- find costovertebral angle and push gently with 1 finger
- no tenderness, tap gently
- Often positive with peylonephritis (chronic inflammation)
- sensitivity 21%
- specificty 88%
Leukocytosis
- High WBC count
- neutrophilia
- monocytosis
- lymphocytosis
- eosinophilia
Most common cause is acute infection
- fever as well suggests infection
- left shift and toxic granualtion suggests even more strongly acute infection
Neutrophilia
An increase in the number of peripheral neutrophils at least 2 standard deviations above the mean
- form of leukocytosis
- seen commonly in acute infection
- also seen in chronic infection
- goes up with cancer, drugs etc
Monocytosis
leucocytosis
- also with infections
- seen in cancer
- can be found with autoimmune diseases (ex lupus)
- can be found with advanced liver disease (cirrhosis)
Lymphocytosis
- elevated with stress and terror
- infections can cause
- CLL
Eosinophilia
elevated Eosinophil count
- goes us with parasitic infection
- allergies
- could be malaria if coming back from Africa
- sometimes with cancers (hodgkins)
Left Shift
when immature neutrophils are found on a blood smear
- called left shift because we draw the progression of maturation with less mature on the left and more mature on the right
- steroids – can cause neutrophilia (increased mature not immature)
- acute infection – causes left shift including bands
- with severe infection (sepsis) – see mylocytes
- chronic myloid leukemia (CML) - extended left shift including blasts
DO NOT mistake for AML or ALL which would include only mature leukocytes and blasts not the whole array
WBC homeostasis - Response to infection
infection –> organism engulfed by phagocytic cells (neutrophils and macrophages) –> macrophages emit cytokines to recruit more inflammatory cells –> macrophages give off C-CSF and GM-CSF (promote growth of WBC) –> infection cleared
Eosinophilia
- goes us with parasitic infection
- allergies
- could be malaria if coming back from Africa
- sometimes with cancers (hodgkins)
WBC homeostasis - Response to infection
infection –> organism engulfed by phagocytic cells (neutrophils and macrophages) –> macrophages emit cytokines to recruit more inflammatory cells –> macrophages give off C-CSF and GM-CSF (promote growth of WBC) –> infection cleared
Myloproliferative Neoplasms MPNs
- clonal disorders arising in HSC
- indolent and chronic
- excessive production of normal cells in blood and bone marrow
Four main MPNs.
- Chronic mylogenous leukemia (CML)
- polycythemia vera (PV)
- Essential thromobocythemia (ET)
- Primary myelofibrosis (PMF)
(last 3 are disorders of JAK2)
Chronic Myloid Leukemia (CML)
- rare clonal bone marrow disease
- associated with philadelphia chromosome
- BCR-ABL gene fusion (present in 100% of cases)
- asymptomatic leukocytosis
- extended left shift
- presense of basophils
- includes splenomegaly (may be massive)
- blood film that looks like bone marrow has just entered the blood
- disease of older adults (rarely seen in <30)
- more in men than women
Natural History
- not treated –> accelerated development that culminates in blast crisis in 3 years
Treatment
- tyrosine kinase inhibitor
- imatinib
- Dasatinib
- nilotinib
- busitinib
- ponatinib
(resistance can occur)
BCR-ABL
CML
- translocation of t(9;22) philadelphia chromosome (causing BCR-ABL gene fusion) –> BCR-ABL protein is a tyrosine kinase with altered specificity –> phosphorylation causes CML
CML
- Presence of BCR-ABL is the gold standard diagnosis of CML
CML Therapy
- specific tyrosine kinase inhibitors are used to treat CML
- drugs bind the ATP binding pocket of BCR-ABL prevents acquisition of Phosphate for phsophorylation –> phsophorylation cannot occur and leukemia is not caused
-
Polycythemia Vera
- primary erythrocytosis
- mutations in JAK2 or CALR
- splenomegaly
- hgih hemoglobin
- Thrombosis risk (think, blood so thick it doesnt flow)
- 5% of these patients go on to develop CML
- treat with aspirin and phlebotomy (bleed them out)
Erythrocytosis
primary - polycythemia vera
- activating mutation of JAK2 (its on all the time, constantly causing RBC development)
secondary erythrocytosis
- caused by problem in heart or lung
- reduced SaO2 –> blood gets to kidneys and stimulates release of Epo –> Epo goes to bone marrow, activated JAK2 and
- low –> increased erythropoiesis
Esential Thrombocythemia
- increased platelets
- mutation in JAK2 CALR MPL
- big spleen
- hight platelet count
- some thrombosis and bleeding risk
- very low AML risk
Treat with aspirin
primary myelofibrosis
- also a platelet disorder
- mutations in JAK 2 and CALR
- big spleen full of hematopoetic cells
- constitutionak symptoms
- early - moderate increase in WBC
- late - pancytopenia (bone marrow becomes fibrotic bc of fibrotic factors secreated by megakaryocytes)
Febrile Neutropenia
- Medical Emergency (the more comorbidities an individual has the more dangerous this is)
- scarce neutrophils –> eaily clearable infection can develop into sepsis
- treat with broad spectrum antibiotics and then narrow afterwards
Approach to patient with Febrile Neutropenia
- is patient hypotensive?
- YES - maintain BP –> Saline bolus –> ICU
- NO -
- physical exam, find site of infection
- culture blood, urine, sputum, CXR
- Initiate broad spectrim antibiotic therapy
General Approach to All Emergencies
ABCDEFGH
A - airway/C-spine - patent? Protected?
B - breathing (is air going in and out?)
C - Circulation - pulse? BP?
D - disability - conscious, bleeding , pain?
E - Examine - quick survey: skin, imbs, lines, drains
F - Fluids - get an IV
G - Get
H - Help
