Haematology 2

Question 1

Myeloproliferative disorders/neoplasms:

• Definition
• Types
• Complications
• Symptoms
• Signs

Answer 1

Myeloproliferative disorders:

• Definition: involves the uncontrolled proliferation of a single type of sc. Associated with. mutations in JAK2, MPL, CALR. They are considered a form of cancer occurring in the bm although tend to progress slowly. They have potential to develop into acute myeloid leukaemia
• Types:
  1. Primary myelofibrosis
  2. Polycythaemia vera
  3. Essential thrombocytopenia/thrombosis
• Complications: myelofibrosis (prolif of a single cell leads to fibrosis/scar tissue. This causes cytokines to be released from these cells such as fibroblast GF. Fibrosis affects blood cells production leading to pancytopenia. This also causes extramedullary haematopoiesis (liver + spleen) hence megaly/portal htn/sc compression
• Symptoms: assymp, fatigue, weight loss, night sweats, fever
• Signs: Anaemia signs, splenomeg, Portal htn (ascites/varices/abdo pain), bleeding/petechiae (low platelets), raised hb (itching, headachees, red face), recurrent infections (low wbc), gout

Question 2

Primary myelofibrosis:

• Definition
• Risk factors
• Symptoms
• Signs
• Investigations
• Management

Answer 2

Primary myelofibrosis:

• Definition: a myeloproliferative disorder of haemopoietic scs causing marrow fibrosis
• Risk factors: >65yrs old
• Symptoms: weight loss, fever, night sweats, abdo pain/early satiety (splenomeg), marrow failure (infections, bleeding, anaemia), hepatomeg, bone pain
• Signs: splenomeg
• Investigations: blood film (poikilocytes (tear shaped rbcs), leucoerythroblastic), bloods (fbc (low hb, high platelets/wcc, pancytopenia occurs later), bm trephine biopsy (aspiration may be dry as the bm has turned into scar tissue) (fibrosis, hypercellular tissue, reduced fat space, inc reticulin staining, tear drop poikilocytes), JAK2/MPL/CALR genes testing
• Management: if minimal symptoms no active treatment, supportive (treat anaemia, splenomeg, portal htn), chemo hydroxycarbamide, targetted therapies jak2 inhibitors ruxolitinib, allogenic sc transplant possibly curative if <70 + fit

Question 3

Essential thrombocytosis/thrombocythaemia:

• Definition
• Symptoms
• Signs
• Investigations
• DD
• How to distinguish this from other causes of high platelets
• Management
• Complications

Answer 3

Essential thrombocytosis/thrombocythaemia:

• Definition: myeloproliferative disorder caused by dysregular megakaryocyte (platelet precursor) prolif hence sustained elevated platelets with a tendency for thrombosis and haemorrhage. Most common in F 50-70yrs and survival 10-15yrs
• Symptoms: 50% assymp, incidental blood finding (platelets >450 x109/l), jak2 mut distinguishes if prim or secondary, thrombosis, bleeding (intracranial, gi), headache, dizzy/syncope (hyperviscosity)
• Signs: splenomeg, hyposplenism (if multiple infarcts), erythromelalgia (red/blue discolouration of extremities + burning), livedo reticularis (a netlike pattern of reddish-blue skin discoloration due to swollen bv)
• Investigations: bloods (fbc (raised platelets, no basophilia and without evidence of reactive causes such as iron def/inflamm), evidence of clonal marker jak2/calr/mpl, bm trephine biopsy (hypercellular marrow + megak clumping, reticulin not increased)
• DD:
  1. secondary thrombocytosis: triggered by infection (acute is EBV, CMV, chronic is tb, toxoplasmosis), iron def, trauma/surgery, cancer, inflamm
  2. Polycythaemia vera
  3. CML
  4. Primary myelofibrosis
  5. Myelodysplastic syndromes
• How to distinguish this from other causes of high platelets
• Management: if high risk chemo hydroxycarbamide to control disease + aspirin to reduce thrombus formation. If low risk just aspirin
• Complications: thrombosis (mi, stroke, vte)

Question 4

Polycythaemia vera:

• Definition
• Symptoms
• Signs
• Investigations
• DD
• How to distinguish this from other causes of high hb
• Management
• Complications

Answer 4

Polycythaemia vera:

• Definition: also known as primary prolif polycythaemia. A type of blood cancer where there is proliferation of erythroid cells (erythrocytosis) resulting in high hb making blood thicker, most common >40
• Symptoms: headaches, visual changes, fatigue, dizzy, chest pain, itchy skin, sweaty, redness of hands/feet/burning (erythromelalgia), cold extremities, joint pain, abdo pain, bleeding (due to impaired platelet function)
• Signs: ruddy/red complexion, conjunctival plethora, splenomeg, htn
• Investigation: pulse oximetry (2ndary?), bloods (fbc (haemocrit (>0.52M, >0.48F) + fbc raised, epo low, in some raised wbc/platelets, u+es, urate, serum ferritin to exclude iron def), raised red cell mass test + low plasma vol study (look at amount rbc + plasma cells), epo, bm biopsy (hypercellular bm), genetic jak2 v617f/mpl/calr testing, uss spleen
• DD:
  1. Secondary polycythaemia: due to excess EPO (COPD/high altitude (chronic hypoxia), anabolic steroids, renal cancer) (neuts/platelet counts normal)
  2. Relative polycythaemia: due to low plasma vol (dehyd, alc, diuretics, pyrexia, D+V)
  3. Essential thrombocytosis: Splenomeg less freq, jak2 mut less common, epo normal, isolated thrombocytosis (absence of inc hb)
  4. CML: thrombosis less common, philadelphia chromo transloc
• Management: venesection, aspirin to reduce thrombus formation, chemo hydroxycarbamide to control disease
• Complications: thrombosis (mi, stroke, vte), gout (inc uric acid in blood when lots of cells are broken down)

Question 5

Myelodysplastic syndromes:

• Definition
• Risk factors
• Symptoms
• Investigations
• Management

Answer 5

Myelodysplastic syndromes:

• Definition: rare blood cancer where mutation in myeloid cells in bm resulting in inadeq and ineffective haematopoiesis so don’t have enough healthy blood cells. Has a potential to transform into acute myeloid leukaemia
• Risk factors: old age, previous chemo/radio
• Symptoms: assymp, incidental blood finding, anaemia signs, neutropenia signs, thrombocytopenia signs
• Investigations: fbc (pancytopenia), blood film (blasts), bm biopsy
• Management: watchful waiting, supportive (blood/platelet transfusions), erythropoietin, granulocyte colony stim factor stims neuts, chemo, targeted therapy, allogenic sc transplant

Question 6

• Function of spleen
• Definition of splenomegaly
• Causes of splenomegaly - severe, mod, mild
• Investigations for splenomegaly
• Asplenia
• Hyposplenism causes
• Hyposplenism management

Answer 6

• Function of spleen: largest lymphoid organ.

1. It filters blood removing old/damaged rbcs via phagocytosis
2. Filters and destroys encapsulated bacteria (neisseria meningitidis, haem influ, strep pneum) in blood + produces T cells 25% and 15% B cells
3. Plays a role in extramed haemopoesis
4. Pools blood so they can be used during bleeding

White pulp involved in immune response, red pulp is storage site for platelets and contains mO to remove rbcs.
Part of the reticuloendothelial system (part of immune system made up of monocytes and tissues containing phagocyte cells to remove damaged cells + foreign ag

• Definition splenomegaly: considered enlarged when can be palpated 2cm below the costal margin or imaging shows its size is above upper limits. Can lead to splenic rupture as no longer protected by ribcage
• Causes of splenomegaly:

Massive:
1. Infiltration of cells - myeloproliferative disorders (CML, AML, myelofibrosis)
2. Tropical infections - malaria or HIV

Moderate:
1. Myeloprolif disorders, lymphoprolif disorders (CLL, lymphoma, amyloidosis)

Mild:
1. Myelo and lymphoprolif disorders
2. Portal HTN due to hepatic cirrhosis, portal vein htn, splenic vein thrombosis, right heart failure
3. Infectious causing overwork - infectious mononucleosis EBV, septicaemia due to encap bacteria

To determine cause bloods (fbc, lfts, liver screen, autoimmune screen, crp, cultures), hiv test, viral serology, CXR (bihilar lymphadenoapathy = lymphoprolif), malaria film if travel, CT if malig suspected, bm aspirate/lymph node biopsy

Give them abx therapeutic/abx, blood transfusion, chemo, low dose chemo for palliation if haematological problem, and signif or rupture splenectomy with vaccination to reduce risk postsplen infection

• Asplenia: lack of a functional spleen - congen or acquired due to splenectomy therefore immunocompromised so lifelong prophylactic abx, immunisations and annual flu
  This patients have falsely high HbA1C because red cells have higher lifespan to become more glycosylated
• Hyposplenism causes:

1. Splenectomy: due to trauma or cancer
2. Sickle cell disease causing infarcts/fibrosis
3. GI disease (IBD, coaeliac)
4. Autoimmune (SLE, RA, hashimotos)
   Blood film shows howell jolly bodies (DNA remnants bc not removed by spleen)

• Management:
  Patients must be immunised (vaccines are pneumococcal, meningococcal, h influenzae, influ annual) and given lifelong abx prophylaxis

Question 7

• Functions of lymphatic system
• Lymphadenopathy definition
• Causes of lymphadenopathy
• What to ask in history
• Examination
• Investigations

Answer 7

• Function of lymphatic system: transport excess interstitial fluid from peripheral tissue to systemic circ (right lymphatic duct drains right half of upper body/thoracic duct does rest), absorbs fat sol vitamins, immune system function (APC + lymphocytes in nodes, thymus, tonsils, spleen, peyers patches)
• Lymphadenopathy definition: lymph node enlargement >1cm
• Causes of lymphadenopathy:

1. Infection - viral (EBV, CMV, HIB, childhood diseases (MMR, varicella), hsv, hep), bacterial (aures, pyogenes, tb), fungal, parasitic
2. Inflammation - lupus, RA
3. Malignancy - ALL, lymphoma, mets (breast, lung, thyroid)
4. Medications - allopurinol, atenolol, cephalosporins, phenytoin
5. benign idiopathic

• What to ask in history: squittars (onset, changed, what does it feel like/hurt, any other regions, recent infection), systemic symptoms of ca, risk factors (unprotected sex, drugs, foreign travel, chemical exposures), meds, surgical, fam hx,
• Examination: size, consistency, fixation, tenderness, signs of underlying disease (throat, pallor conjunctiva, hepatosplenomegaly, bruising)
• Investigations: bloods (fbc, crp, ldc cultures), blood film, swabs, USS/CT, lymph node biopsy

Question 8

Amyloidosis:

• Definition
• Causes
• Symptoms
• Investigations
• Management

Answer 8

Amyloidosis:

• Definition: a complex group of disorders caused by deposition of extracellular insol fibrils composed of misfolded proteins in organs + bv leading to organ damage. More common in M, 50-70yrs
• Causes:
  Primary = deposition of monoclonal light chains from abnormal plasma cells in tissues and occurs spont or in assoc with multiple myeloma or waldenstroms macroglobulinaemia
  Secondary = caused by other disorders
  Can cause systemic AL (deposits throughout body, systemic AL occurring in 10% pts with myeloma) or focal (cerebral deposition in alzheimers)
  Can also be auto dom inherited via familial amyloid polyneuropathy
• Symptoms:
  1. Kidneys - nephrotic syndrome, renal failure
  2. GI - macroglossia, malab, hepatosplenomeg
  3. Neurological - neuropathies
  4. Vasculature - periorbital purpura
  5. Joints - large joint inflamm
  6. Heart - cardiomyopathy
• Investigations: tissue biopsy shows apple green birefringence when stained with congo red and viewed under polarised light, ecg, 24 hour urine collection for proteinuria, serum free light chains/Igs, PT/APTT
• Management: amyloid AL: dexmethasone, bortezomib and measure serum free light chains to assess response

Question 9

Immune thrombocytopenia purpura ITP

• Definition
• Risk factors
• Symptoms
• Investigations
• Management

Answer 9

• Definition: immune mediated reduction in platelets due to antibodies against glycoprotein IIb/IIIa
• Risk factors: older females
• Symptoms: incidental on bloods, petechiae/purpura, bleeding, haemorrhage
• Investigations: bloods (fbc - low platelets), antiplatelet ab (igG), blood film ,bm aspirate (megakaryocytes)
• Management: oral pred, IVIG if active bleeding or urgent invasive procedure, splenectomy if platelets <30 after 3 months of steroids, immunosuppressants cyclophosphamide