Haematology Flashcards
- Severe nose bleeds and post-surgery bleeding (predominantly mucosal bleeding)
- Autosomal dominant inheritance
- Mildly elevated APTT
What is the provisional diagnosis and what test would confirm this??
Mild type 1 vWF deficiency
Confirm via blood tests for:
vWF Ag levels
vWF activity or function tests
- X-linked inheritance
- Characterised by joint bleeding! (often post-trauma)
- Mildly elevated APTT
What is the provisional diagnosis and what test would confirm this?
Mild Type Haemophilia
Confirm via blood tests for factors 8 (deficiency=Type A) and 9 (deficiency=Type B)
And/or genetic tests
- Bruising and petechiae on skin +/- Blood blisters on palate/mucosal surfaces, epistaxis, menorrhagia, GI bleeding, intracranial bleeding…
- Previously well with no medications
- Only abnormality on investigation is thrombocytopenia
What is the provisional diagnosis?
Treatment for this?
Immune Thrombocytopenia Purpura (ITP)
Diagnosis of exclusion!
Make sure to do FBE, blood film, U&Es, LFTs (can lead to renal failure), ANA, serology for EBV & CMV
Treatment:
- High dose steroids
- IV Ig if bleeding
- Splenectomy if life-threatening bleeding
- DO NOT give plts
- Arterial or venous blood clots
- Mixing study not correctable - what does this mean and what further bloods would you order for diagnosis?
What is the provisional diagnosis ?
indicating presence of an inhibitor rather than factor deficiency
-Blood tests positive for anticardiolipin and antiphospholipid Ab
Antiphospholipid syndrome (primary or secondary to SLE or induced by drugs such as Quinine)
- HX severe trauma, obstetric complications, sepsis, allergic/toxic reaction, cancer
- Investigations reveal: Low Hb and Plt; high APTT and PT; low fibrinogen; positive D dimer
What is the provisional diagnosis ? What is the underlying pathophys?
Disseminated Intravascular Coagulation
Widespread activation of clotting cascade results in formation of clots in microvasculature around body, leading to organ infarct and coagulation factor deficiency which leads to bleeding at other sites.
Causes microcytic anaemia
Iron deficiency (slow chronic bleed or nutrient deficiency)
Anaemia of chronic disease
Thalassaemia
Causes normocytic anaemic
Hypoproliferative
- leukaemia
- aplastic anaemia
- pure red cell aplasia
Hyperproliferative
- haemmhorage/bleed
- haemolytic anaemia (sickle cell, thalassaemia, spherocytosis, G6DP deficiency, haemolytic uraemia, DIC, TTP)
Causes macrocytic anaemia
Megaloblastic
-B12/folate deficiency
Non-megaloblastic
- cirrhosis, liver failure
- alcoholism
- myelodysplastic syndrome
- congenital bone marrow failure syndrome
- myeloproliferative disorders
- myeloma
What are 2 common causes of acute decline in CML?
Developing Largre B Cell lymphoma
Infection from immunocompromised state (few white cells)
Casues of mediastinal obstruction
- Massive lymphadenopathy
- Thyroid (neoplasm or goitre)
- Thymus (neoplasm)
- Teratoma (germ cell neoplasm)
- Terrible lymphoma (lymphoma or lymphoblastic)
What is the name of the cells characteristically found on Hodgkins lymphoma histopath?
Reed Sternberg cells.
35 year old female w erythema nodosum, SOB (CT chest shows pulmonary nodules)
What are 2 probable diagnoses and what histo path pattern would you see on biopsy?
Sarcoidosis or Tb.
Granulomatous inflammation on biopsy.
Pathophys of ITP
Patient develops autoantibodies for glycoprotines (Ag) on platelet membranes -> platelets targeted to the spleen for sequestration -> destroyed (phagocytosed) by mononuclear macrophages
Signs and symptoms of ITP
Petechiae and ecchymoses
Gingival bleeding
Haemorrhagic bullae
Occurs in otherwise healthy person (no splenomegaly, wasting, signs of chronic disease/infx)
MX ITP
Prednisone + IV Ig
DO NOT infuse platelets - they will be destroyed by immune response!
DDX for petechiae/purpura/ecchymosis
- Thrombocytopenia
- ITP
- Secondary to meds, leukaemia, SLE, APL syndrome, vWF deficiency - Vascular disorders
- Senile purpura, HTN, Henoch Schonlein purpura - Coagulation problem
- DIC or Scurvey - MENINGOCCOCEMIA
Extrinsic pathway:
- which blood test measures this?
- what drug acts on this pathway?
- INR /PT
2. Warfarin
Intrinsic pathway:
- which blood test measures this?
- what drug acts on this pathway?
- APTT
2. Heparin
What is primary haemostasis?
How do you test this?
Vasoconstriction, platelet adhesion and activation via binding vWF, and pletelet aggregation to form plug.
Triggered by exposure of collagen and subendothelial matrix from vessel injury
Test via platelet count.
WHat is secondary haemostasis and how do you test it?
Reinforcement of platelet plug by formation of fibrin meshwork via extrinsic and intrinsic pathways.
How does the extrinsic pathway differ from intrinsic pathway in how they start, and where do yhey join up with the common pathway?
Extrinsic: starts w tissue damage & exposure of Tissue factor
Intrinsic: starts with conversion of factor 12 to 12a
Common pathway: conversion of factor 10 to factor 10a
How long does clopidogrel stay in system for?
10-12 days. essentially a long-acting aspirin
What can you do for bleeding due to drugs?
- dabigatran
- warfarin
- clopidogrel/aspirin
- prothrombinex and activated factor 7
+ antidote for dabigatran - give vitamin K, Or FFP and prothrombinex
- Give platelet transfusion (aspirin and clopidogrel affect platelets for extent of life span) and FFP
Differentials for abnormal bleeding
Haemophilia A or B vWF disorder Other factor deficiency Platelet disorder Anticoag/antiplatelet drugs
Investigations to order for bleeding disorders
FBE - plts, Hb
Coags
Factor VIII, IX levels (factor 8 levels give indicator of vWF levels; haemophilia A and B)
vWF Ag
vWF activity or function test
Blood group (group 0 have lower levels vWF)
Genetic studies
Type 1 vs Type 2 vWF deficiency
type 1- partial deficiency
type 2-complete vWF deficiency
Treatment for vWF disease
Treat only if symptomatic
Desmopressin - releases stores of vWF and factor 8
OR replacement therapy (recombinant factor 8/vWFAg concentrate or recombinant vWF Ag or cryoprecipitate)
Antifibrinolytics to symptomatically treat tranexamic acid
What are the hallmarks of haemophilia?
X linked (in males)
Haemarthrosis
Subcutaneous and intramuscular haematomas
Poor wound healing
Abnormal APTT but normal INR (factor 8 and 9 only involved in intrinsic pathway)
Treatment of haemophhilia
Replace factor 8 or 9
Treatment of DIC
Treat the underlying cause
REsusitation and resp/circ support
Cryoprecipitate - rich in blood factors
Causes of DIC
cancer obstetric complications massive tissue injury sepsis transfusion reaction Large aortic aneurysm Severe allergic/toxic reaction
Causes of B12 deficiency
Absorption of B12 requires gastric acid and IF
- Atrophic gastritis (autoimmune - autoantibodies targeting IF)
- Pancreatic failure
- Post-gastrectomy -lack IF
- Crohn’s or resection of ileum
- Coeliac
- Vegan diet
What causes folate deficiency anaemia?
Alcoholics
Malnourished patients
Pregnancy
What is myelodysplastic syndrome? Who gets it and what might it progress on to?
Haemopoietic stem cell disorders resulting in ineffective production of one or more blood cell lines - fail to mature properly
90% cases over 60
May progress onto AML
What type of anaemia does myelodysplasic syndrome cause?
Macrocytic
Symptoms of anaemia
Fatigue, weakness
Dizziness, syncome
SOB, decr exercise tolerance
Palpitations, tachycardia
THings to ask about on anaemia history
Bleeding, menstruation Systemic/chronic illness Family HX Medications (L-DOPA, penicillin, quininine, NSAIDs, paracetamol) Diet, alchohol
Clues to haemolytic anaemia
Incr red cell breakdown:
- incr bilirubin, urinary urobilinogen
- incr serum LDH
Incr red cell production
- incr reticulocytes
Extravascular
-splenomegaly
Intravascular
- incr free plasma Hb
- decr plasma Haptoglobin
- Haemoglobinuria (red-brown urine )
- haemosiderinuria (occurs after haptoglobin binding capacity is exceeded)
What is the most common leukaemia in children?
ALL
What is the most common acute leukaemia in adults?
AML
What is the most common leukaemia?
CLL
What syndrome is associated with ALL?
Down syndrome and Fanconi’s anaemia
Acute vs chronic leukaemia pathophsy
Acute- overproduction of malignant IMMATURE WBCs (Blasts)
Rapidly multiply in bone marrow, suppressing normal function and spill into blood crowing out healthy cells.
CHRONIC: abnormal WBC blasts fail to die and accumulate in blood, bone marrow and related organs
What cells are affected by AML and CML?
erythrocytes, mast cells, thrombocytes (plt), basophils, neutrophils, eosinophils, macrophages and monocytes
What cells are affected by ALL and CLL?
ALL - B cells, T cells, NK cells
CLL- B cells mostly
What is myeloma?
Neoplastic disease of plasma cells (Ab producing mature B lymphocytes)
Neoplastic plasma cells produce PARAPROTEIN (abnormal Abs consisting of light protein only)
SX of myeloma
Calcium levels high
Renal failure - proteinuria
Anaemia (tiredness and fatigue)
Bony pain (back pain, fractures) - lytic lesions on x-ray
(CRAB)
What is Lymphoma?
Neoplastic disease of mature lymphocytes in lymphoid tissue (lymph nodes, spleen, tonsils, MALT)
What is Leukaemia?
Acute - Neoplastic disease of IMMATURE cells (blasts) in bone marrow. affects myeloid or lymphoid progenitor cells
Chronic - neoplastic disease of MATURE white blood cells in the bone marrow.
Affects more mature cells
You have too many WCCs but they are dysfunctional so immune function is impaired.
Which leukaemia might transform into which other leukaemia?
CML may transform into AML (blast crisis)
what is Myeloproliferative disease. name 3 examples
Neoplastic proliferation of platelets, RBCs or fibroblasts (everything other than WBCs)
- RBCs: polycythaemia rubra vera
- Plts: Essential thrombocythaemia
- Fibroblasts: myelofibrosis
What is myelodysplastic syndrome?
Pre-cancerous disease of bone marrow here dysplastic cells may cause abnormal or inadequate blood cell production. May progress to acute leukaemia.
Often occurring in old people.
Often results in anaemia, thrombocytopenia, requiring regular blood transfusions.
How does MM lead to lytic bony lesions?
neoplastic plasma cells increase osteoclastic activity and reduce osteoblastic activity via secretion of inflammatory IL cytokines -> leads to bone breakdown and hypercalcacemia
What is the protein in the urine from MM called?
Benz Jones protein
How does MM lead to renal failure?
Paraprotein (M protein) or free light chains in blood can deposit in organs and cause dysfunction
Investigations for MM
BMAT
Bone marrow biopsy
Xray (osteoporosis) and CT (bony lesions)
Blood and urine:
- FBE
- UEC and BUN
- Electrophoresis looking for paraprotein and urinary Bence jones protein
What are Auer Rods a sign of?
AML (almost sounds like auer)
Which leukaemia is the philidelphia chromosome associated with and what does this indicate?
CML in all cases.
ALL in some cases.
Philadelphia chromosome: t(9,22) causing production BCR-ABL gene which makes tyrosine kinase enzyme which leads to CML
Indicates good prognosis due to drug (TK inhibitors (imatinib) selectively kill CML cells)
Symptoms/signs of Leukaemia
- SX of anaemia - dizzy, SOB, fatigue, tachycardia etc (decr RBC)
- Easy bleeding, bruising (decr Plts)
- Freq infections, slow healing (defective WBCs)
- Lymphadenopathy (lumps)
- Hepatosplenomegaly
- GUM HYPERTROPHY + bleeding WITH AML
- MASSIVE splenomegaly with CML
- Weight loss, night sweats with CML and CLL
Investigations for Leukaemia
Blood film
FBE
Coags
Bone marrow aspirate
What leukaemia are smear/smudge cells (on blood film) associated with?
CLL.
Which leukaemia are more associated with old people?
CML and CLL.
What are reed-sternberg cells characteristic of?
Hodgkin’s lymphoma
What does high LDH indicate in lymphoma, leukaemia?
High risk of CNS involvement and tumor lysis
How do you diagnose lymphoma?
Core or excision biopsy of lymph nodes (or other lymphoid tissue involved)
What is the Ann Arbour staging system used for? What are the stages and how do you determine this.
Hodgkin and non-hodgkin lymphoma
Determine stage via CT/PET and BMAT 1. Confined to single lymph node region
2. 2/more nodal areas involved on same side of diaphgragm
3. Nodes on both sides of diaphragm involved
4. Spread beyond lymph nodes (liver, bone marrow etc)
◊ Every stage is either
A: no systemic symptoms present other than pruritis
B: systemic symptoms (fever, night sweats, weight loss) present
Worse disease
How might Hodgkin’s lymphoma present?
YOUNG person.
Enlarged rubbery lymph nodes non-painful
Becomes tender after drinking alcohol
Systemic symptoms
May get SVC obstruction SX from mass effect
What are examples of low grade (1) and high grade (2) non-hodgkin lymphoma
Which has best cure rates?
Low grade: Follicular lymphoma
-Indolent course but often wide-spread at diagnosis so non-curable.
High grade: Diffuse large B cell lymphoma, Burkitt lymphoma
-Best cure rates because more aggressive but treatable.
what is MGUS?
Low levels of serum monoclonal protein with NO EVIDENCE of end-organ damage (no CRAB)
When does myeloma become symptomatic?
> 10% malignant monoclonal plasma cells in bone marrow and/or tissue biopsy
Myeloma-related organ dysfunction (CRAB) present.
What will serum and urine electrophoresis in MM show?
□ Low IgG (2/3) and IgA (1/3)
□ High serum free light chains (free kappa and free lambda)
□ High paraprotein/M protein (Ig produced by a single clone of plasma cell)
= “Bence Jones protein” in urine
Treatment of MM
Chemotherapy and radiation
Bisphosphonates
Transfusions and epo (anaemia)
May need dialysis if end-stage RF
Anaemia with rouleaux on blood film with unexplained hypercalcaemia, renal failure and fracture/bony pain. What do you suspect?
Multiple myeloma
