Haemathology Flashcards
(66 cards)
1
Q
What’s the leukaemia that presents with these features:
Children, Pain (mostly bones), easy bruising
(hepatosplenomegaly is common)
A
Acute Lymphoblastic Leukaemia
2
Q
What’s the leukaemia that presents with these features:
Gingival hypertrophy
Leukaemia cutis,
civd,
Organomegaly less frequent,
Lymphadenopathy rare
A
Acute myloid leukaemia
3
Q
What’s the leukaemia that presents with these features:
-» Lymphadenopathy
65yo, insidious, lymphocytosis
A
Chronic lymphocitic leukaemia
4
Q
What’s the leukaemia that presents with these features:
Massive splenomegaly, leukocytosis (low blast count)
Generally asymptomatic
A
Chronic myeloid leukaemia
5
Q
What’s the disease that presents withs
Auer’s rods in bone marrow biopsy?
A
AML
6
Q
Most common leukaemia in senior adults (>70y)?
A
Chronic Lymphocytic
CLL
7
Q
Most common leukaemia in children?
A
Acute lymphocytic
ALL
8
Q
Investigation of ALL
A
- Characteristic blast cells on peripheral smear and bone marrow (diagnostic!)
- Normal blasts on BM ➔ < 5%, in ALL ➔ 50-99%
- CXR and CT (to rule out mediastinal, abdominal lymphadenopathy)
- Lumbar puncture to rule out CNS involvement
9
Q
What’s the most likely leukaemia to present with mediastinal mass in adolescents?
A
ALL
10
Q
Diagnosis and treatment of ALL?
A
- 30% lymphoblasts (French American British classification) OR
- 20% lymphoblasts (WHO classification)
- present in the bone marrow (+/- peripheral blood blasts)
Chemotherapy, Radiotherapy, Bone marrow transplant
11
Q
Diagnosis and treatment of CLL
A
Picture of asymptomatic lymphadenopathy PLUS blood exam findings:
* Absolute lymphocytosis
* Smudge cells on peripheral blood
* T-cell surface antigens (Flow cytometry)
TTO
* Observation (watch and wait)
* Stern cell transplant
* Chemotherapy
12
Q
Investigation of CLL
A
- TLC ➔ 10,000 - 15,000 with absolute lymphocytosis (100% of the time!)
- Bone marrow aspirate and biopsy not required for diagnosis
13
Q
Indication of cryoprecipitate?
A
Is primarily composed of fibrinogen and factor VIII. So in case of Fibrinogen deficiency. For example, DIC or liver failure.
14
Q
Indication of washed PRC (PACKED RED CELLS)
A
IgA deficient recipients and patients with allergic or febrile reactions to transfusion.
15
Q
Considerations about transfusion in IgA deficient recipients?
A
They may have anaphylactic reactions to plasma containing IgA. So blood for IgA deficient recipients is often sourced from IgA deficient donors
16
Q
Tranfusional acute haemolytic reaction management and causes
A
ABO mismatch
- hypotension, tachypnoea, back or chest pain
- Stop infusion and administrate normal saline through new IV line
- Perform diret antigen test in the recipient blood
17
Q
Febrile non-haemolytic transfusion reaction manegement and causes
A
Fever withouth jaudice or orther symptoms. In a severe form, rigors and pulmonary infiltrates
Happens due to reaction with donor leukocytes and an incompatibility of human leukocyte antigens (HLA).
No specific therapy is needed and the transfusion may continue.
18
Q
What’s the most likely cause of anaphylatic reaction to transfusion?
A
IgA deficiency
19
Q
What’s the most common presentation of allergy to transfusion?
A
Urticaria. Usually ceased with antihistamine,
- If pior allergy, use washed cellular components
20
Q
Time to trigger TRALI symptoms
A
Within 6 hours of the beginning of administration of any blood product containing donor plasma.
21
Q
TRALI features
A
Acute respiratory distress mediated by the aggregation of recipient leukocytes in the lung parenchyma. It presents as hypoxia or dyspnoea within 6 hours of the beginning of administration
22
Q
Pathophysiology of TRALI
A
Related to donor anti-HLA antibodies which bind recipient leukocytes.
Donors who are at risk of causing TRALI have been sensitized to the HLA molecules of foreign leukocytes – typically woman who have been pregnant or donors who have previously been transfused themselves.
Transfusion of blood products containing donor plasma from previously pregnant women should be avoided!
23
Q
When can an O- cause haemolytic reaction to a recipient?
A
In the rare Bombay phenotype
The ABO backbone ‘H’ is not expressed, there cannot be an ABO or RhD mismatch between donor and recipient
24
Q
When can an O- cause haemolytic reaction to a recipient?
A
In the rare Bombay phenotype
The ABO backbone ‘H’ is not expressed, there cannot be an ABO or RhD mismatch between donor and recipient
25
Main features of ALL
Acute
Blast predominate
Common in Children
Drastic course
Elderly (2nd peak incidence)
Few mature WBCs cause Fevers
26
In ALL, what's the meaning of the following markers in the flow cytometry analysis?
CD19
CD3
CD16 and CD56
TCR
MHC II
CALLA
All is mostly related to positive CD10 and CD24. CD 20 and CD34 expression is variable
CD19 and MHC II - indicate that cells belong to B cell/lymphocites family
CALLA (CD10)- pro-B cells
TDT indicates immature lymphocites (pre-B or pre-T)
CD2, CD3, CD5, CD7, CD8 and TCR are present on T cells.
(CD3 indicates complex T cell)
CD16 and CD56 are present on NK cells. Not linked to ALL
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Why ALL sometimes presents with dysphagia in children?
Tymus enlargement due to leukemic infiltration
28
What are the typical markers of B cell envolvement in ALL?
CD19, CALLA (CD10), MHC II
29
Bone marrow biopsy shows 25% of blasts. Diagnosis?
Leukaemia
If >35%, ACUTE leukaemia
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Prognostic factors for leukaemia?
Age of onset (Worst children < 1y or >10Y OR adults >60y)
Degree of WBC count (>50000)
Failure in achieving complete remission in 4 weeks
T-cell lineage is worst than B cell and more rare
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Tumor lysis syndrome serum findings
Elevates: K, phosphate, Uric Acid
Decreases: Calcium
+ Lactic Acidosis
Urate crystal deposition in the collecting tubules -> present in urine before acute renal failure
32
Treatment sections of ALL
Induction
Consolidation
Maintenance
CNS prophylaxis
33
What's the main treatment for AML promyelocitic form (APL)
All- trans retinoid acid (ATRA)
If failed, consider TMO
34
Most common cytogenetic abnormality in AML?
t (8;21) (q22;22), present in 5-12%, mostly AML with maturation (M2)
35
What's the most common complication of APL / AML
CIVD
36
AML prognostic signs
Good:
t(15;17)
t(8;21)
inv(16)
Bad:
Antecedent of myelodysplasic syndrome
Hyperleucocytosis
Older age
Prior cytotoxic therapy for other malignancies
37
Genetic abnormality in CML
Philadelphia chromosome, an abbreviated chromosome 22, t(9;22)(q34;q11).
The chromosome contains the BCR-ABL1 fusion gene (from ABL1 on chromosome 9 and BCR on chromosome 22), which induces constitutive tyrosine kinase activation and consequently, uncontrolled granulocyte production.
38
Phases of CML
Chronic - initial, indolent symptoms, TTO WITH TYROSINE KINASE IHIBITOR (TKI - DESATINIB, NILOTINIB)
Accelerated -
Blast chrisis
39
Lab findings in CML
Important leukocytosis with neutrophils predominance and immature circulating cells
40
In CLL, what's the meaning of the following markers in the flow cytometry analysis?
CD5, CD19, CD20 and CD23
TdT
Positive for CD5, CD19, CD20 and CD23
Negative for TdT
CD19 is related do B cells, not only present in CLL, but also ALL.
41
Difference between CLL and Monoclonal B cell lymphocytosis?
In MBL, absolute lymphocyte count is < 5000.
42
What's CLL treatment?
If asymtomatic, WATCHFULL WAINTING (no pharmacotherapy).
If symtomatic (generally, B symptoms):
Ibrutinib (TKI)
Vernetoclax (BCL2 inhibitor)
Rituximab (monoclonal antobodies)
43
Autoimmune complications are common in CLL. What's the most important ones?
Autoimmune haemolytic anaemia (AIHA) is the MOST COMMON complication and doesn't affect overall pronogsis. Treatment with glucocorticoids and Rituximab
Autoimmune haemolytic anaemia (ITP) is the LESS COMMON.
!If ITP + AIHA -> Evan's syndrome
44
The most dangerous complication of CLL?
Diffuse large B cell lymphoma.
It happens through Richter's transformation.
Rapid progression of adenopathy, systemic B signs, rise in LDH with normal bilirubin
45
Haemochromatosis - genetic overview
Autosomal recessive pattern of inheritance
Mutation in the HFE gene.
46
Schitocytes (helmet cells) - occurence
Schistocytes (helmet cells) are fragmented erythrocytes.
They occur in microangiopathic hemolytic anemias, such as:
- Disseminated intravascular coagulation
- Hemolytic-uremic syndrome
- Thrombotic thrombocytopenic purpura
- Due to erythrocyte destruction by prosthetic cardiac valves.
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Hemolytic anaemias - lab characterization
Hemolytic anemias are characterized by:
- decreased serum haptoglobin level
- increased lactate dehydrogenase
- increased bilirubin (mostly indirect)
48
Haptoglobin - overview
Haptoglobin is an acute-phase reactant whose principal clinical utility is in defining conditions of hemolysis.
Its levels can also become elevated in infection and inflammation.
Haptoglobin is used as an acute-phase marker of red blood cell (RBC) destruction. Its value decreases and may even be absent when RBCs are destroyed at twice the normal rate.
> Decreased or absent haptoglobin levels are seen in the following conditions:
Intravascular hemolysis (hereditary spherocytosis, pyruvate kinase deficiency, autoimmune hemolytic anemia, transfusion reactions)
Extravascular hemolysis (intraperitoneal hemorrhage)
Intramedullary hemolysis (thalassemias, sideroblastic anemias, megaloblastic anemias)
Genetics (haptoglobin is absent in 1% of whites and 4%-10% of blacks)
Cirrhosis
Infancy
Pregnancy
Burns
> Increased haptoglobin levels are seen in the following conditions: [2, 3]
Diseases associated with elevated erythrocyte sedimentation rate (ESR) (acute-phase reactants) such as infection, trauma, inflammation, hepatitis, amyloidosis, collagen diseases, or lymphoma and leukemia
Obstructive or biliary diseases
Steroid use
Aplastic anemia
Diabetes mellitus
Smoking
Nephrotic syndrome
Increased estrogen level
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Acute hemolytic transfusion reaction - overview
Pathogenesis
ABO incompatibility
Intravascular hemolysis
Clinical findings
Onset within minutes to 24 hours of transfusion
Fever, chills, hypotension
Hemoglobinuria, flank pain
Laboratory findings
Positive direct Coombs test
Hemolysis (eg, ↑LDH, ↑indirect bilirubin)
Complications
Acute renal failure
Disseminated intravascular coagulation
50
Patients with CKD and bleeding tendencies - Diagnosis
Platelet dysfunction
Clinical features
Easy bruising
Mucosal bleeding (eg, epistaxis, GI hemorrhage)
Dx can be established with a normal platelet count and normal coagulation studies.
CKD have disruption of primary hemostasis, including platelet–von Willebrand factor (vWF) interactions.
As levels of urea (the end product of ammonia breakdown) rise, its precursors are shunted to a different pathway that leads to nitric oxide production. Inappropriately high nitric oxide results in decreased platelet adhesion, activation, and aggregation
Symptomatic patients are typically treated with desmopressin (DDAVP), which stimulates the release of vWF and reduces bleeding time.
51
Polyciythemia vera - overview (clinical findings, Diagnosis)
Polycythemia vera (PV) is a clonal myeloproliferative disorder characterized by erythrocytosis.
> Most cases are associated with a JAK2 mutation. Patients are often asymptomatic at diagnosis but may present with symptoms related to increased blood viscosity (transient visual disturbances, hypertension, thrombosis) and increased red blood cell (RBC) turnover (gouty arthritis).
Manifestations
↑ Blood viscosity
Hypertension
Erythromelalgia (burning cyanosis in hands/feet)
Transient visual disturbances
↑ RBC turnover (gouty arthritis)
Aquagenic pruritus
Bleeding
Examination
Facial plethora (ruddy cyanosis)
Splenomegaly
Laboratory findings
>> Complete blood count often shows an increase in all 3 cell lines.
Low erythropoietin level
JAK2 mutation positive
Complications
Thrombosis
Myelofibrosis & acute leukemia
Treatment
Phlebotomy
Hydroxyurea (if ↑ risk of thrombus
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Von Willebrand Disease (vWD) - cf, epidemiology
Causes inadequate platelet adhesion and secondary deficiency of Factor FVIII
F=M, Family history
Easy bruising, bleeding from mucous membranes (particularly epistaxis->10 min, oral mucosa, menorrhagia) and post-op bleeding, (bleeding after dental procedures, tonsillectomy).
Type 2N presents with the bleeding is due to low factor VIII levels and mimics the findings seen in classical hemophilia, including soft tissue, joint, and urinary bleeding, and bleeding after invasive procedures.
Type 2B; with thrombocytopenia.
Type 3, both mucocutaneous and soft tissue bleeding as well as joint bleeding
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Von Willebrand Disease (vWD) - ix, ttx
Ix:
FBE, PT/Aptt, fibrinojen: Aptt long, Plt: Normal/low.
Diagnosis: Initial tests
Plasma von Willebrand factor (VWF) antigen (VWF:Ag)
Plasma VWF activity (ristocetin cofactor activity, VWF:RCo and VWF collagen binding VWF:CB)
Factor VIII activity (FVIII)
54
Haemophilia - types, genetics
Haemophilia is an X-linked bleeding disorder affecting ~ 1 in 7000 males.
Haemophilia A is Factor VIII (8) deficiency.
Haemophilia B is Factor IX (9) deficiency (Christmas disease).
DxT spontaneous haemarthrosis + muscle bleeds + delayed bleeding =haemophilia A
APTT prolonged, Normal prothrombin time and fibrinogen.
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Haemophilia - bleeds requiring admission
Suspected intracranial haemorrhage
Bleeding into neck/throat
Forearm/calf bleed with suspicion or evidence of compartment syndrome
Bleeding into hip or inguinal area, suspected ileopsoas haemorrhage
Undiagnosed abdominal pain
Persistent haematuria
Bleeds causing severe pain
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Haemophilia - bleeding ttx
joint and muscle bleeds: RICES
Desmopressin (DDAVP):
Releases stored Factor VIII (and von Willebrand factor) into the circulation.
Used in patients with mild haemophilia A. Not used in major bleeds.
Generally not recommended in young children ( < 3 years) due to documented reports of hyponatraemia and seizures
Antifibrinolytic therapy (tranexamic acid):
Reduces breakdown of blood clots and is effective for treating and preventing recurrence of mouth bleeds and epistaxis.
Contraindicated for treatment of haematuria!
57
Henoch-schonlein purpura (HSP) - Dx and Ix
Diagnosis: Clinical!
Urinalysis is required.
Check BP! If hypertension, macroscopic haematuria or significant proteinuria detected : Send urine for formal microscopy and protein-creatinine ratio (UPCR), and bloods for urea/electrolytes/creatinine (UEC) and albumin.
Ix for DDx or complications:
FBE (Normal, PT,APTT: N), UEC, albumin
Blood and urine culture
Abdominal imaging( USG), to exclude Intussusception!
ANA, dsDNA, ANCA, C3/C4
Biopsy of affected organ(skin, kidney) demonstrating predominantly Ig A deposition supports diagnosis if required.
58
Henoch-schonlein purpura (HSP) - C Fx
HSP is the most common vasculitis of childhood.
2-8 years of age.
Cause is not known.
50% preceded by a history of a recent upper respiratory tract infection.
HSP is characterised by palpable purpura with arthritis/arthralgia (~50-75%), abdominal pain (~50%) and/or renal involvement (~25-50%) (haematuria/proteinuria/hypertension).
Skin (painful subcutaneous oedema), diffuse alveolar haemorrhage, neurologic(labile mood, apathy, hyperactivity, encephalopathy, intracranial haemorrhage), testicular torsion is rare.
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Henoch-schonlein purpura (HSP) - Acute and chronic managements
Acute Management:
Mild pain with subcutaneous oedema and join pain, no other complications, diagnosis is clear: Bed rest at home, close follow up by GP, analgesics( Paracetamol or short course NSAIDS)
Moderate-severe pain - The use of steroids (glucocorticoids) has been shown to reduce the duration of abdominal and joint pain. It does not effect long-term renal complications! Give as long as symptoms persists.
Long-Term Management
Initial urinalysis is normal or only microscopic haematuria, review clinically and check BP/early morning urinalysis at these recommended time intervals:
Weekly for the first month after disease onset
Fortnightly from weeks 5-12
Single reviews at 6 and 12 months.
If there is no significant renal involvement plus normal urinalysis at 12 months, no further follow-up is required!
60
Henoch-schonlein purpura (HSP) - When to admit and red flags for renal complication
Admit if:
Serious abdominal complications
Severe debilitating pain
Severe renal involvement (see ‘discussion with Nephrology’ under ‘Follow-Up’ below)
Neurological involvement
Red flags for renal complications which may require kidney biopsy or immun-supression:
Hypertension
Abnormal renal function
Macroscopic haematuria for 5 days
Nephrotic syndrome
Acute nephritic syndrome
Persistent proteinuria
61
Henoch-schonlein purpura - what to remember of management and prognosis
Urinalysis is the only investigation required in a classic presentation of HSP. Further investigations may be required if the diagnosis is unclear, abdominal or with renal involvement.
Mostly self-limiting and require only symptomatic management.
Close follow-up for renal involvement requiring intervention. Such renal involvement can be asymptomatic.
Prognosis:
A first episode of HSP, in the absence of significant renal disease, usually resolves within 4 weeks. The rash is usually the last symptom to remit.
Joint pain and uncomplicated abdominal pain resolves in 2-3 days.
In 25-35% of patients , HSP reccurs in 4 months.
Kidney complications occurs mostly in 2 months time, can be seen in 6 month.
62
Why is it necessary to evaluate the skeletal system in multiple myeloma patients, and what imaging methods are recommended for this purpose?
Evaluation of the skeletal system is essential to determine the size, number, and location of bone lesions in multiple myeloma (MM) patients, which aids in predicting symptomatic progression. 🦴📈
In the past, plain radiographs (skeletal survey) were used for this purpose, but now cross-sectional imaging with whole-body CT, MRI, or positron emission tomography (PET) scan is recommended due to their higher sensitivity. 📷🩺🚀
63
What is the preferred screening modality for evaluating the skeletal system in multiple myeloma patients, and why?
In most centers, the preferred screening modality for evaluating the skeletal system in multiple myeloma is a whole-body low-dose CT scan without contrast. 🏥📷
This choice is based on its relatively low cost and the ease and speed of testing. 💰🕒
64
What is the pathophysiology and clinical presentation of symptomatic cholelithiasis in pregnant women?
Pathophysiology involves increased biliary cholesterol excretion due to elevated estrogen levels and decreased gallbladder motility because of elevated progesterone levels. 🔄🌡
Clinical presentation includes recurrent, postprandial epigastric/right upper quadrant (RUQ) pain. 🍽️🩺
65
How is symptomatic cholelithiasis in pregnancy diagnosed, and what is the recommended management?
Diagnosis is confirmed with RUQ ultrasound, which may reveal gallstones or biliary sludge as echogenic foci within the gallbladder. 📷🧩
Management during pregnancy is typically conservative, focusing on pain control because most cases resolve with supportive care. 🤰🏥
Cholecystectomy is usually delayed until the postpartum period for complicated or recurrent cases. ⏳👩⚕️
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