Haematology

Red cells, white cells, platelets, plasma (protein rich fluid that suspends all the blood components containing coagulation factors, albumin, antibodies)

Hb levels for females [115-155], males [130-170]

Mean corpuscular volume: [80-99]

WBC = [4-11 * 10^9/L]

Platelets: [150-400* 10^9/l]

Usually 280ml / unit, stored at 4 degrees celsius, stored for up to 35 days

stored at room temperature, constantly agitated. shelf life of 7 days due to risk of bacterial infection. 1 pool for 4 donors is standard adult dose

stored at -30 degrees, shelf life of a year. must thaw for 20-30mins before use and give ASAP within 1 hour before coagulation factors degenerate. usual dose of 12-15 ml/kg. need to know blood group

from FFP thawed at 4-8 degrees overnight. contains fibrinogen, vWf and factor 8. stored the same as FFP. standard dose is from 10 donors.

Indicated in massive bleeding and fibrinogen is very low.

Type O (universal donor): no antigens present but anti-A / B

Type B: b antigens, anti- A

Type A: a antigens, anti-B

Type A+B (universal recipient): A / B antigens, no antibodies

RhD = rhesus +ve (antigen present)
Rhd = rhesus -ve (no antigen)

request, sample, sample receipt, testing, component selection, labelling, collection, prescription, administration

Always check for positive patient ID

variation in the size of RBCs

central pigemented area surrounded by a pale area, surrounded by a ring of thicker cytoplasm on the outside

seen in IDA, post-splenectomy, sickle cell, thalassaemia, coeliac disease

seen in myelofibrosis

seen in IDA

individual blobs inside RBC’s due to denatured globin

seen in G6PD and alpha thalassaemia

blobs of DNA material inside RBCs that are normally removed by the spleen

seen in post-splenectomy, severe anaemia where body is regenerating RBCs too quickly

immature RBCs that are large and still have RNA material inside

seen in haemolytic anaemia

fragments of RBCs indicating physical damage from trauma during their journey in the blood vessels

seen in haemolytic uraemic syndrome, metallic heart valves, haemolytic anaemia

immature RBCs containing iron, when the bone marrow is unable to incorporate iron into haemoglobin

ruptured WBCs seen in process of preparation of the blood film due to frail / aged WBCs

seen in chronic lymphocytic leukaemia

spherical RBCs without normal bi-concave disk

seen in autoimmune haemolytic anaemia or hereditary spherocytosis

CELLULAR DAMAGE stimulates the release of tissue factor to combine with factor 7 to become factor 7a. activated factor 7 then actives factor 10 for the common pathway

SUB-ENDOTHELIAL CONTACT due to damage on vascular endothelium activates intrinsic pathway along with thrombin from previous cascade.

Factor 12a activates 11. Factor 11a activates 9.

9a + 8a + 5 + calcium and platelet membrane phospholipid activates factor X.

+ve feedback loop were thrombin production activates intrinsic pathway

factor 10 activated by extrinsic / intrinsic pathway leads to factor 2 (prothrombin) being turned into factor 2a (thrombin). Thrombin combines with factor 1 (fibrinogen) to activate it = 1a [fibrin]

converts fibrinogen into fibrin. Also iniiates +ve feedback loop via the intrinsic pathway. Thrombin activates platelets via their receptors to cause aggregation and thrombin causes fibrin to crosslink to generate a ‘fibrin mesh’ which creates a thrombus = stops bleeding

binding of thrombin to vascular endothelium produces protein C. This activates protein S which breaks down factor 5a and 8a which are needed for thrombin generation.

Antithrombin is also produced by the liver to destroy factor 11a, 10a, thrombin. [Heparin / fondaparinux enhances antithrombin effect]

Warfarin is a vitamin K antagonist where vitamin K is needed for the synthesis of factors 2,7,9,10. Vitamin K is also needed for natural anti-coagulation factors like protein C / S so warfarin may initially inhibt their production = more clotting initially

forms the basis of INR where PTT tests the extrinsic pathway [7,10,2,1]. PTT measures the time taken for fibrin to form via the extrinsic pathway. Normal is 9-12 seconds

Prolonged PTT causes: disseminated intravascular coagulation, vit K deficiency, chronic liver disease

Measures the time taken for fibrin to be formed via intrinsic pathway. normal is 23-38 seconds. therefore measures factors 12,11,9,8,10,5,2,1

Prolonged APTT causes: disseminated intravascular coagulations, clotting factor deficiencies, vWf disease, lupus anticoagulants

PT measuring does not take into account that there are large amounts of thrombin in +ve feedback loop in circulation so with even small amounts of factor 7, it can bring about haemostasis

APTT can be interfered via lupus anticoagulants [phospholipid antibodies] which prolong APTT BUT do not increase patients tendency to bleed

X linked recessive condition. Haemophilia A is a deficiency in factor 8
Haemophilia B is a deficiency in factor 9

patients can bleed excessively to minor trauma and are at significant risk of spontaneous haemorrhages. Most cases occur in neonates / early childhood (intracranial haemorrhages, haematomas, cord bleeding).

Haemarthroses (spontaenous bleeding into joints) and muscles is indicator for severe haemophilia. Untreated = joint damage + deformity

prolonged APTT BUT bleeding time, thrombin time, prothrombin time NORMAL

can use genetic testing and coagulation factor assays as well

replace affected clotting factors via IV infusions in acute episodes of bleeding / bleeding prevention in surgery

in addition, give desmopressin to stimulate vWf release + antifibrinolytics

formation of antibodies to clotting factor = treatments becomes ineffective (10-15% of haemophilia A px develop antibodies to factor 8 Tx)

most common inherited abnormal bleeding disorder. Autosomal dominant. vWf is a carrier molecule for factor 8 which is needed for the intrinsic pathway activation of factor 10

Type 1: partial reduction of vWf (80% of patients)
Type 2: abnormal form of vWf
Type 3: total lack of vWf (autosomal recessive)

FHx of heavy bleeding, Hx of unusually easy, prolonged, heavy bleeding. bleeding gums w/ brushing, epistaxis, menorrhagia

based on history
prolonged bleeding time but platelets are normal. APTT may be prolonged. Factor 8 can be reduced.

desmopression (increases vWf and factor 8) for acute cases of major bleeding / surgery prep, to increase vWf release. Can also be infused alongside factor 8 concentrate.

Can give COC pill, tranexamic acid for menorrhagia. Hysterectomy for severe cases

Acquired disorder, may be primary or secondary to SLE. Presence of antiphospholipid antibodies which makes blood become prone to clotting = HYPERCOAGUBLE STATE [paradoxical rise in APTT]

Strongly associated with SLE and other autoimmue isorders

DVT / PE history. Stroke, MI, renal thrombosis history. Problems with pregnancy (recurrent miscarriage, stillbirth, pre-eclampsia), livedo reticularis (purple rash on skin, mottled appearance)

Thrombocytopenia. Paradoxical rise in APTT due to ex-viro reaction of lupus anticoagulant autoantibodies involved in coagulation cascade. Will see lupus anticoagulant, anticardiolipin antibodes (these cause prolonged APTT)

Primary thromboprophylaxis (no thrombotic events) = low dose aspirin
Secondary: initial VTE with lifelong warfarin [INR 2-3], recurrent VTE [INR 3-4]
Pregnant women = LMWH (enoxaparin) and aspirin

DOACs ARE NOT RECOMMENDED

Most common inherited thrombophilia where there is function mutation in factor 5 leiden protein which leads to factor 5 being inactivated 10 times slower by activated protein C than normal [ACTIVATED PROTEIN C RESISTANCE] = makes you more hypercoaguble

Homozygous is a 10x VTE risk, heterozygous is 4-5x risk

hepatic vein thrombosis usually seen in background of polycythaemia vera, thrombophilia, pregnancy, COC pill

will see sudden / severe abdo pain, ascites, tender hepatomegaly

Investigate via US with doppler scan

direct thrombin inhibitor, renally excreted. reversed via idarucizumab

direct factor 10a inhibitor, excreted by liver, reversed by andexanet alfa

direct factor 10a inhibitor, excreted faecal, reversed by andexanet alfa

direct factor 10a inhibitor, faecal excretion, no reversal authorised yet

IV route, activates antithrombin 3 for inhibit thombin, 10a,9a, 12a.

SEs: bleeding, heparin induced thrombocytopenia, osteoporosis. Monitor via APTT

reversed by protamine sulphate

SC injection, long acting, activates antithrombin 3 to inhibit factor 10a

SEs: bleeding, heparin induced thrombocytopenia, osteoporosis

monitor via anti-factor 10a

heparin exposure leads to antibodies [anti platelet factor 4 antibodies] developed against platelets. forms a complex with platelets to activate clotting mechanism and thombus = thrombocytopenia and unexpected thrombus development

Diagnoseed via HIT antibodies in blood. Stop heparin and use alternative anticoagulant

Blood clots (thrombi) can develop in circulation, usually secondary to Virchow’s triad. These thrombi can emoblise and travel from deep veins and into RHS of heart / lungs, blocking pulmonary arteries (PE). If thepatient has an atrial septal defect, blood clots can pass through LHS of heart and into systemic circulation = into brain, causing a stroke

immobility, recent surgery / hospitilasation, long travel, pregnancy, advancing age, obesity, FHx of VTE, central venous catheter

SLE, malignancy, thrombophilia, HF, antiphospholipid syndrome, Behcets, nephrotic syndrome, sickle cell disease

COC, HRT, raloxifene, tamoxifen, antipsychotics

every patient should be assessed for VTE. prophylaxis via LMWH / fondaparinux or unfractionated heparin for CKD px. May also use anti-embolic compression stockings, these are contraindicated in cases of PAD

CI: active bleeding, existing coagulation

usually unilateral, below the knee. Will see calf swelling, rubor, dilated superifical veins, tenderness and oedema, Examine via measuring calf circumstance betwen the two, difference >3cm is significant.

Wells score, if >2 then DVT likely = request proximal leg vein US within 4 hours followed by a D-dimer test

Everything is 1 point:
active cancer, paralysis / paresis of lower extremities, recently hospitalised or bedridden for > 3 days, localised tenderness in calf, entire leg swollen, >3cm swelling compared to other leg, pitting oedema, collateral superifical veins, previous DVT

if there is an alternative diagnosis that is at least as likely as DVT = -2 points

1st line: apixaban / rivaroxoban. If this is not suitable = LMWH + dabigatran / edoxaban for 3 months before deciding if VTE was provoke or unprovoked.

if patient has stage 5 CKD OR antiphospholipid syndrome = LMWH and vitamin K antagonist.

do a risk assessment at first booking and following admission. previous VTE is high risk and needs LMWH until 6 weeks postnatal. Avoid DOACs and warfarin in pregnancy.

Look at lymphocyte count. If low = should be AML or CML.

If WBC > 100 = think chronic so CML

If presence of band cells = CML

if presence of blast cells = AML

cancer of the bone marrow resulting in unregulated production of one type of cell can lead to suppression of other cell types = pancytopenia

classified as either acute / chronic and myeloid / lymphoid

anaemia + leukopenia + thrombocytopenia

Acute lymphoblastic leukaemia = <5yrs, > 45yrs

Chronic lymphocytic leukaemia = > 55yrs

Chronic myeloid leukaemia = >65yrs

Acute myeloid leukaemia = >75yrs

very non-specific sx:

fatigue, fever, failure to thrive, pallor, petechia (abnormal bruising due to thrombocytopenia), abnormal bleeding, lymphadenopathy, hepatosplenomegaly

take a FBC within 48hrs of suspected leukaemia, look at blood film for abnormalities, LDH may be raised. Can look at CXR for infection / lymphadenopathy, lymph node biopsy, lumbar puncture, CT / MRI / PET for staging

Definitive method is bone marrow biopsy.

MDT meeting for chemo / radio therapy. Surgery, bone marrow transplant

mostly affects children, associated with downs syndrome and philadelphia chromosome.

It is the acute proliferation of usually B lymphocytes which causes pancytopenia via suppression

anaemia [lethargy, pallor], neutropenia [frequent, severe infections], thrombocytopenia [easy bruising, petechiae]

may also see bone pain, hepatosplenomegaly, fever, testicular swelling

Investigated via blood films will show blast cells

age < 2 yrs or >10yrs. WBC >20, T / B cell surface markers, male, non-caucasion

most common in adults. can be a result from a myeloproliferative disorder like polycythaemia vera / myelofibrosis. Just keep in mind that there are many different types, all with different presentations

anaemia, thrombocytopenia, neutropenia, bone pain, fevers, hepatosplenomegaly

blast cells but these are not specific

>60yrs, >20% blasts after first course of chemo, cytogenetics (deletion of chromosome 5 / 7)

philadelphia chromosome presence: this is the translocation of genes from chr 9 and 22. ABL proto-oncogene from 9 fuses with BCR genes in 22. Forms BCR-ABL fusion protein which upregulates tyrosine kinase activity

often ASx. Can see infections, anaemia, bleeding, weight loss. Splenomegaly, autoimmune haemolytic anaemia, lymphadenopathy, increase in granulocytes with blast transformations.

Usually incidental finding with px having these sx > 5yrs

Imatinib is 1st line = inhibits tyrosine kinase

Hydroxyurea / interferon alpha can also be used. Bone marrow transplant

in adults = chronic proliferation of B-lymphocytes

often incidental, anorexia / weight loss, bleeding / infections, lymphadenopathy, anaemia / infections

blood film will show smear / smudge cells from fragile WBCs. Immunophenotyping is a key investigation

Lymphomas are the cancerous proliferation of lymphocytes within lymph nodes to become abnormally large = lymphadenpathy

To tell between non-Hodgkins and Hodgkins, you need to do a biopsy looking for Reed-Sternberg cells

HIV, epstein-Barr virus, autoimmune conditions like RA / sarcoidosis, FHx

lymphadenopathy (enlarged lymph nodes in the neck, axilla, inguinal region). Fever, weight loss, night sweats, itching. Normocytic anaemia, eosinophilia, recurrent infections

Lymph node biopsy to see for abnormally large B cells with multiple nucleus that have nucleoli inside them “owl face appearance” = Reed-Sternberg test

LDH may also be raised but this is non-specific. CT / MRI / PET to diagnose / stage lymphoma and other tumours

Can also take a histological sample to see for nodular sclerosing and mixed cellularity [both have good prognosis]. Lymphocyte predominant is the best prognosis. Lymphocyte depletion is the worst prognosis

Lugano staging system:
Stage 1 = confined to one lymph node or region
Stage 2 = 2 + lymph nodes in more than one region but confined to either below or above the diaphragm
Stage 3 = affects lymph nodes both above and below diaphragm
Stage 4 = widespread involvement of non-lymphatic organs

chemotherapy regime [ABVD = doxorubicin, bleomycin, vinblastine, dacarbazine]. Radiotherapy, combined modality therapy (chemo followed by radio).

Haematopoietic cell transplantation for relapsed / refractory Hodgkins.

6th most common cancer in UK, more common than Hodgkins. typically px > 75yrs.

Will see maliganant proliferation of lymphocytes accumulation in lymph nodes and other organs

HIV, h pylori, hep B or C, exposure to pesticides, FHx, immunodeficient like DM or transplant recipient, autoimmune diseases

similar to hodgkins, only differentiated by lymph node biopsy. painless lymphadenopathy [non tender, rubbery, asymmetrical], classic red flag sx of weight loss, fever, night sweats

investigate via biopsy = “starry sky appearance”. CT for staging. test for HIV. normocytic anaemia, LDH, Lugano staging

dependent on subtype of specific non-hodgkins lymphoma. Routine flu / pneumococcal vaccines. ABx prophylaxis. Screen for hepatitis B

Rituximab, stem cell transplantation

Usually triggered by chemotherapy / steroid treatment. Break down of tumour cells relases uric acid into the blood. Uric acid can form chemicals in the intersitial tissue and tubules of the kidneys leading to AKI. Will see hyperK, hyperPhosphate with hypoCa

Abnormalities in findings with background of chemotherapy within the past 3 days or post-7days [Cairo Bishop scoring]: needs 2+ of

Uric acid > 475, K > 6mmol/L, phosphate > 1.125mmol/L, Ca < 1.75

will also see high serum creatinine, possible cardiac arrhythmia and sudden death, seizures

IV allopurinol immediately prior or during chemotherapy. Can give raspuricase as an alternative but not given together

Cancer of the plasma cells that produce antibodes, so you will see large quantities of a single type of antibody [monoclonal paraprotein]. Caused by genetic mutation. Usually you will see IgG proliferation.

RFs: older age, male, black-Aftrican, FHx, obesity

Calcium elevated due to increased OC activity.
Renal failure due to increase in antibodies blocking flow through tubules.
Anaemia.
Bleeding [thrombocytopenia].
Bone lesions due to infiltration of plasma cells and OC activity, typically in skull, spine, long bones, ribs. Leads to increased risk in pathological fractures
Infection due to reduced production of normal Ig leads to increased susceptibility to infections.

You can also see hyperviscosity of the plasma due to more proteins {IgG} in the blood. Leads to easy bruising / bleeding, loss of sight, purple discolouration, HF

have a high suspicion in px > 60yrs with bone / back pain that does not improve. You will see anaemia, thrombocytopenia, hyperCa, ESR, plasma viscosity.

Monoclonal protein band in serum or urine electrophoresis [Bence-Jones proteins]. Bone lesions, End organ damage like renal insufficiency. Increased plasma cells on marrow biopsy.

Whole body MRI / CT/ Xray to see lytic lesions, “raindrop appearance” on skull

Induction therapy for autologous / allogenic stem cell transplantion AFTER chemotherapy to remove px of their own stem cells.
Bortezomib + Dexamethasone + thalidomide
Usually for younger, healthier px who are more suitable. Monitor px every 3 months post treatment. If relapses = Bortezomib is first line.

Can give bisphosphonates to suppress OC activity. Orthopaedic surgery for fractures, cement augmentation into vertebral fractures / lesions to improve stability / pain

Used for transfusion in chronic anaemia and cases where infusion of large volumes of fluid may result in CVS compromise

Patients who are thrombocytopaenic, are bleeding or require surgery

adminstered to patients with thrombocytopenia

contains clotting factors, albumin, immunoglobulin. Used to correct clotting deficiencies in patients with hepatic synthetic failure who are due to undergo surgery.

Formed from supernatant of FFP. Rich source for fibrinogen and factor 8. indicated for massive haemorrhage or uncontrolled bleeding due to haemophilia.

only platelets can be ABO incompatible in adults. Everything else needs to be cross matched

collects px own blood lost during surgery and re-infuses it. One type can clear blood prior to reinfusion to reduce risk of contamination.

Advantages: saves donor blood, reduces risk of blood borne infections, may be more acceptable for Jehovah’s witness

CI for maliganant disease for risk of faciliatating disease dissemination.

stop warfarin, give vitamin K (IV takes 4-6hrs to work), give FFP only if human prothrombin complex is not available.

Cytomegalovirus is transmitted in leucocytes so most blood products are now leucocyte depleted so CMV -ve products are rarely needed UNLESS in granulocyte transfusions.

Irradiated to have no T-lymphocytes in order to avoid transfusion associated graft vs host disease causes by engraftment of viable donor T lymphocytes

1. anaphlaxis,
2. acute haemolytic transfusion reaction,
3. delayed haemolytic transfusion reaction,
4. febrile non-haemolytic,
5. transfusion related acute lung injury, 6. transfusion associated circulatory overload

can be caused by px w/ IgA deficiency who have anti-IgA antibodies.

Will see hypotension, dyspnoea, wheezing, angioedema, urticaria / hives, pruritus

Stop the transfusion, give IM adrenaline, oxygen, fluids, consider corticosteroids / anti histamines

ABO-incompatible blood, e.g secondary to human error.

Will see fever, abdominal pain, hypotension, Hb released into blood so jaundice, AKI and haemoglobinuria

Stop transfusion, confirm diagnosis via checking px identity and the bag, repeat direct Coombs test, repeat typing and cross matching. Give fluid resuscitation

haemolysis > 24hrs due to minor antigens in donor blood like Rhesus +ve. Results from anamnestic (previously exposed) response like previous exposure to these antigens beforehand from prior transfusion or pregnancy. Antibodies mark donor RBCs for destruction by the reticuloendothelial system

may be ASx, can see mild fever / jaundice

caused by antibodies with WBC fragments in the blood product like cytokines

Fever, chills

Slow / stop transfusion, paracetamol, monitor

non-cardiogenic pulmonary oedema secondary to increased vascular permeability caused by host neutrophils that become activated by substances in donated blood.

hypoxia, pulmonary infiltrates on xray, fever, hypotension

stop transfusion, give oxygen and supportive care

excessive rate of transfusion + pre-existing heart failure.

pulmonary oedema, HPTN

slow / stop transfusion, consider IV furosemide and oxygen

transmission of vCJD but this is now very rare

seen in weeks or months where there are no preformed antibodies. Results in hypersensitivity reaction where there is dense interstitial lymphocytic infiltrate in grafts tissue and vasculitis seen on histology

will see fever, malaise, peripheral oedema, HPTN, oliguria

months or years, where the recipients antigen presenting cells present graft antigens to recipient CD4 T helper cells leading to a gradual immune response. Will see proliferation of vascular SM, parenchymal atrophy, intersitial fibrosis

May see chronic allograft nephropathy, bronchiolitis obliterans, accelerated atherosclerosis, vanishing bile duct syndrome

CANT BE PREVENTED OR TREATED

type 4 hypersensitivity reaction, common in grafts that are rich in lymphocytes. T lymphocytes from immunocompetent donor and cells from immunocompromised host leads to severe organ dysfunction

Will see maculopapular rash on palms / soles, hepatosplenomegaly, diarrhoea / abdo pain, dyspnoea, muscle cramps / weakness

Prevent by irradiating blood products to kill lymphocytes or may be on purpose to kill tumour cells

sepsis, B12 / folic acid deficiency, liver failure, leukaemia, myelodysplastic syndrome (BM cancer)

sodium valproate, methotrexate, PPIs, antihistamines. heparin induced thrombocytopenia, haemolytic uraemic syndrome, Immune thrombocytopenic purpura in adults

heparin induced, drug induced, alcohol, liver disease, hypersplenism, viral infection (EBV, HIV, hep), pregnancy, SLE / antiphospholipid syndrome, B12 deficiency

often incidental and presents ASx

you may see spontaneous brusing / prolonged bleeding times, nose / gum bleeding, heavy periods, blood in urine / stool

antibodies against platelets (glycoprotein 2b,3a complex) causing an immune response = less platelets

will see bruising, petechiae, purpura, epistaxis, bleeding

Investigations via FBC will show isolated thrombocytopenia

give oral prednisolone (1st line), IV immunoglobulins IF situation is urgent, rituximab, splenectomy.
Educate patient when to seek help, monitor platelets, control BP, suppress menstrual periods.

[international normalised ratio] measures blood coagulation via taking px prothombin time and divide it by normal PT.

major bleeding: stop anticoags, give IV vit. K + prothombin complex

minor bleeding: stop anticoags, give IV vit K, repeat INR after 24hrs

INR > 8 but no bleeding: stop anti coags, give oral vit K, repeat INR after 24hrs

INR > 5 but no bleeding: withold 1-2 doses of anti-coags, review maintenance dose of anti-coags

<3mm patches of non-blanching rashes, caused by burst capillaries

between 3-10mm, non blanching, from leaky blood vessels

flat non palpable lesions <10mm

elevated lesions <10mm that can be felt

myeloproliferative disorder that can be primary {myeloproliferative neoplasm}, or secondary to polycythaemia vera or essential thrombocythaemia, leukaemia, autoimmune disease, toxins like benzene .

It is the proliferation of a cell line leading to fibrosis of the bone marrow. Fibrosis places scar tissue in the BM and affects the production of blood cells = leading to hepatosplenomegaly which can lead to anaemia and low WBCs / portal hypertension

initially ASx, systemic sx (fatigue, weight loss, night sweats, fever)

anaemia (except in polycythaemia), hepatosplenomegaly, portal HPTN, thrombocytopenia, thrombosis, increase in RBCs, less WBCs

Triad of conjunctival plethora (excessive redness), ruddy complexion, splenomegaly

Myelofibrosis may show anaemia, leukopenia / leukocytosis, thrombocytosis / thrombocytopenia

Blood film will show tear drop RBCs, poikilocytosis

Bone marrow biopsy to confirm diagnosis, test for JAK2,MPL,CALR genes

primary myelofibrosis: allogenic stem cell transplant, chemotherapy to slow down and control sx, supportive management for anaemia, splenomegaly, portal HPTN

Myeloproliferative disorder leading to an increase in RBC mass / number, often accompanied by an overproduction of neutrophils or platelets.

Normal kidneys will produce erythropoietin to bind to JAK2, stimulating RBC production. In PV, you will see a mutation in JAK2 which allows it to be active even without the presence of EPO. This leads to eventually the haemopoietic stem cells being worn down / fibrosis and the BM can no longer produce RBCs (“spent phase”)

Triad of conjunctival plethora, ruddy complexion, splenomegaly.

May see vague sx such as headaches, dizziness, tinnitus, visual disturbance due to hyperviscosity.

Pruritus after a hot bath, erythromyalgia (burning sensation in fingers and toes). May see features of gout, arterial / venous thrombosis / hypertension, early satiety / weight loss due to enlarged spleen pressing on stomach

Recommended to perform a FBC / blood film for raised haematocrit / haemoglobin, RBC mass, slight increase in WBCs and platelets, may also see raised uric acid levels.

EPO levels will be low

Bone marrow biopsy to see for JAK2 mutations and increased proliferation of all myeloid cells.

1st line: venesection to remove blood + aspirin

Chemotherapy drugs to slow down disease progression and improve sx: hydroxyurea

Ruxolitinib is a JAK2 inhibitor

Most signficant cause of morbidity / death is thrombotic events

Megakaryocyte proliferation which results in an overproduction of platelets, can be caused by JAK2 mutation or haemopoetic cell receptor mutation. This disease overlaps with chronic myeloid leukaemia, polycythaemia vera, myelofibrosis

Fatigue, headache, dizziness, nausea, tinnitus, numbness in hands and feet. increased risk of thrombotic events, erythromyalgia, splenomegaly BUT NO PRURITUS.

platelet count will be very high [>600], increased risk of haemorrhage / spontaneous bleeding, burning sensation in hands

very high platelet count with possibly high WBC and haemoglobin.
Bone marrow biopsy to see for raised megakaryocytes and JAK2 / CALR mutation. Rule out any reactive thrombocytosis causes like IDA via iron studies

hydroxyurea / hydroxycarbamiide to reduce platelet count. Interferon alpha can be used for younger px. Low dose aspirin to reduce thrombotic rise.

50% caused by JAK2 mutation, 25% by CALR mutation.

Doesn’t always cause a cell count proliferation because it results from abnormal proliferation of megakaryocytes that make cytokines rather than platelets. These cytokines deposit excessive collage in bone marrow which replaces haemopoietic stem cells = anaemia

Classified as MCV < 80. Most common cause is IDA

Other causes: thalaessemia, sideroblastic anaemia, anaemia of chronic disease

typically seen in individuals with chronic inflammatory disease like RA, SLE, Crohns.

Chronic diseases leads to increase in inflammatory cytokines like IL-6 which stimulates hepcidin release. Hepcidin decreases iron absorption via reduced activity of ferroportin which leads to less haemoglobin production due to less iron release from bone marrow = anaemia / reduced RBC survival

Very general sx like fatigue / weakness, SOB on exertion, pallor, tachycardia

reduced serum iron, total iron binding capacity (TIBC) is low. Ferritin levels may be normal / raised due to inflammatory response

px do not respond to oral iron therapy, treatment is via treating the underlying disorder / chronic disease. Recombinant erythropoietin therapy may be considered in cases of renal chronic disease / RA / IBD

autosomal recessive condition where there is a gene defect in Chr 16 causing abnormalities in alpha globin chains resulting in more fragile / easier to break down RBCs. This leads to the spleen to collect a lot more destroyed RBCs leading to swelling / splenomegaly. To compensate for the anaemia, the BM expands to produce extra RBCs which increases susceptibility to fractures = pronounced forehead / cheekbones

fatigue, pallor, jaundice, gallstones, splenomegaly, poor growth / development, pronounced forehead / cheekbones, hypoxia initially due to low RBC count

microcytic anaemia, haemoglobin electrophoresis to diagnose abnormalities, DNA tests, prevention by screening pregant women

monitor FBC and any complications, blood transfusions, splenectomy. Curative is BM transplant

May see features of iron overload due to need of recurrent transfusions and increased absorption of iron in response to anaemia = haemochromatosis features like. Monitor via serum ferritin, limit transfusions, iron chelation (desferoxamine)

autosomal recessive condition that leads to point mutations on chr 11 resulting in abnormal copies that either have reduced function or no function at all of the beta chains.
Reduced / absent beta chains results in the accumulation of free alpha chains in RBCs to clump together and form intracellular inclusions which damage RBC membrane. This leads to haemolysis which leads to haemaglobin to be spill out into the plasma

microcytic anaemia, blood film will show target cells + hypochromia , haemaglobin electrophoresis is the definitive diagnosis (high HbA2)

minor (reduced production of beta chains) = monitoring

intermediate (reduced beta chains) = transfusions and iron chelation may be needed in the future like deferoxamine.

Major (no beta chains) = treat via transfusions, iron chelation, splenectomy, BM transplant

menstruation in women, GI tract blood loss in men. Hookworm infection can cause GI blood loss. Colon cancer bleeding. Gastritis, IBD

pregnant women / growing children have increased demands of iron.

Pregnant women will have increased plasma volume which can cause IDA via dilution

Anything that changes stomach pH as its acidity is needed to absorb iron from duodenum / jejunum in its ferrous state [2+]. These include PPIs, coeliac disease, crohns (inflammation of duodenum / jejunum)

lower income countries, growing children, vegetarians / vegans

fatigue, SOB on exertion, pallor / palpitations, hair loss, atrophic glossitis. oesophogeal webs

Long term features include brittle nails, koilonychia, angular stomatitis, brittle hair, dysphagia / glossitis

history taking is important: diet changes, medication hx, menstrual hx, change in bowel habit, weight loss

Will see microcytic hypochromic anaemia on blood film. Pencil shaped cells, anisocytosis, target cells

Serum iron will be low, TIBC will be high, indicating low iron stores but Transferrin sats will be low. Ferritin can be used but high ferritin can still indicate IDA due to inflammation / cancer / infection

correct underlying cause via investigating using a colonscopy for a cancer. Blood transfusions to correct anaemia. IV cosmofer (iron infusion) can be used but risk of anaphylaxis. Oral iron via ferrous sulphate can be given for 3 months and slowly corrects sx. Will see SE of constipation / black stool. Suggest iron rich diet

look for Hb rise of 10g/L if treating via iron

SEs: nausea, diarrhoea, constipation, poor compliance

X linked / autosomal recessive disease or can be acquire from myeloproliferative disorders, myeloid leukaemia, alcohol misuse, lead toxicity, isoniazids,

It is a deficiency in delta-aminolevulinate synthase-2 which leads to the inabilty of RBC to store / bind iron. This leads to the overall impaired prophoryin synthesis so you will see a build up of iron but not enough haem.

refractory anaemia: anaemia that does not respond to simple haematinic supplementation

hypochromic microcytic anaemia, will see high ferritin / iron / transferrin saturation. Blood film will show presence of sideroblasts with look like a ring of iron accumulation in erythroblasts around the nucleus seen in Perl’s reaction / prussion blue staining

supportive, remove drugs / alcohol if they are responsible. Patients may be responsive to pyridoxine (vitamin B6)

px usually around 30yrs old, it is an acquired condition where there is a reduction in pluripotent stem cells leading to pancytopenia

Causes include: idiopathic, congenital causes like fanconi anaemia / dyskeratosis congenita, drugs (phenytoin, chloramphenicol), benzene toxicity, hepatitis infection, radiation

anaemia, bleeding, infection. easy bruising, bleeding gums, epistaxis. most cases are idiopathic but worth taking a history of drug exposure in last 6 months, occupation exposure, recent infections, comorbidities.

pancytopenia / absence of reticulocytes in FBC. Blood film will show aplastic bone marrow with increased fat spaces and hypocellular

stem cell transplantation for severe cases, younger px and if they have a human leucocyte antigen [HLA] identical sibling donor

Immunosuppressive treatment with antithymocyte globulin and ciclosporin for everyone else.

if both fails, then unrelated matched stem cell transplantation. risk of graft vs host disease

INFECTION is the major concern so you should give broad spectrum parenteral ABx + blood transfusion of RBC / platelets

can be autosomal dominant / recessive / spontaneous mutation.

Results in defects in the red cell membrane which leads to an abnormal RBC. This increases its permeability to sodium which results in more active transport needed to get sodium out of the cell. This causes a change in SA:V ratio of RBC so the RBC becomes more spherical, more rigid which therefore means it cannot pass through splenic microcirculation = reduced lifespan

jaundice, eventual anaemia, gallstones / splenomegaly, aplastic crisis precipitated by parovirus infection. Failure to thrive

mild / severe anaemia. blood film will show spherocytes / polychromasia (blue grey tint on RBC due to being immature). Will see raised serum bilirubin / urinary urobilinogen.

Direct antiglobulin / Coombs test will be negative, excluding autoimmune haemolytic anaemia

nothing specific. occasional transfusion for recurrent infections / pregnancy. consider splenectomy. life long penicillin prophylaxis

autosomal recessive condition where there is an abnormal gene for beta-globin on chr 11. SS = sickle cell anaemia, SC = sickle cell trait (protection from falciparum malaria). This abnormal gene causes polymerisation of the RBC shape in a deoxygenated state leading to sickle cell shape. These cells are fragile + haemolytse which can block small blood vessels = infarction. Haptoglobin will recycle these cells leading to jaundice, gallstones, scleral icterus and low haptolobin levels {intravascular haemolysis sign}

SOCRATES, is this typical pain on sickle pain, any triggers, know your genotype?

past sickle history, frequency / severity of crises, previous complication, previous ITU admission, transfusion past

ask what is their usualy place of care and who is their primary treating consultant

anaemia.
vaso-occlusive “painful crisis”: usually of the hands and feet due to microvascular occlusion leading to severe pain triggered by cold / dehydration / hypoxia. Sometimes cause CNS infarction like stroke, seizures, cognitive defects which needs to assessed by trans-cranial doppler US to assess risk of impending stroke

may see swelling of hands and feet, frequent infections due to sickle cells damaging spleen, visual problems

anaemia, raised bilirubin and reticulocytes. Blood film will show sickle cells, target cells, howell-jolly bodies. Haemoglobin electrophoresis is the definitive diagnosis

for pregnancy / childbirth, offer testing for those at risk of being carries = heel-prick test. Aim for diagnosis at birth via cord blood and give prompt pneumococcal prophylaxis with phenoxymethylpenicillin. Give penicillin prophylaxis for all children with sickle cell, starting at 3 months of age until 5yrs old

Preventative: up to date vaccines, ABx prophylaxis, genetic counselling, parental education

Treat acute crises with paracetamol / NSAIDs ~ escalate to opiods / nerve block. Give oxygen if hypoxic, IV fluids for dehydration

Regular transfusions for px with recurrent severe vaso-occlusive cases. Hydroxyurea therapy

prolonged anaemia can cause increased production of reticulocytes with promotes bone formation of the medullary cavities in the skull = enlarged cheeks

vaso-occlusion = stroke, dactylitis, ACS (vaso occlusion of pulmonary microvasculature), clogging of renal papillae leading to necrosis and nephrotic syndrome, AVN of large joints, retinopathy, pulmonary hypertension

Spleen obstruction = fibrosis leading to splenomegaly increasing risk of hypovolaemia and infections

X linked recessive condition where ATP is required for RBCs to maintain flexibility, regulate their NA/K pumps and keep Hb in a reduced state.
G6PD (glucose 6 phosphate dehydrogenase) converts glucose-6 phosphate into NADPH (nicotinamide adenosine dinucleotide phosphate). NADPH keeps glutathione reduced from oxidised state which protects RBCs from oxidative dmg from hydrogen peroxide.

G6PD deficiency therefore leads to reduced NADPH which reduces reduced glutathione which leads to RBCs being susceptible to oxidation = haemolytic anaemia

Crises are usually triggered by infection, meds like aspirin. primarquine / quinine / chloroquine / quinolones / vitamin K / nitrofurantoin / chloramphenicol OR broad beans / fava beans

look for triggers. presents with neonatal jaundice, gallstones, anaemia, splenomegaly. diagnosis is made via G6PD enzyme assay

blood film will show Heinz bodies and reticulocytes

enzyme assay checked after 3 months of haemolytic attacks to prevent false -ve.

Unable to reduce dyes, most of cells have already haemolysed so will appear normal

stop drugs causing it, treat underlying infection, blood transfusions used

Characterised by the presence in bone marrow of erythroblasts with delayed nuclear maturation due to defective DNA synthesis = megaloblast

Vitamin B12 / folate deficiency or dysfunction causes a block in DNA synthesis due to inability to methylate DUM (deoxyuridine monophosphate)to DTM (deoxythmidine monophosphate) which makes DNA

macrocytic anaemia, thrombocytopenia, neutrophils with hypersegmented neutrophil in blood film. elevated LDH levels

Autoimmune disorder causing antibodies to intrinsic factor and gastric parietal cell bodies leading to B12 malabsoprtion

Features include: progressive weakness, paraplegia, paleness, fatigue, N/V, pins and needles, memory loss / confusion / depression

will see macrocytic anaemia, low vitamin B12, hypersegmented nuclei on blood film. =ve for anti intrinsic antibodies

give cyanocobalamin / IM hydroxycobalamin (vit B12 supplementation). 1mg x3 for 2 weeks and injections every 3 months.

Can increase risk of gastric cancer

folic acid deficinecy usually due to nutrition / diet. Will see megaloblastic anaemia with low serium folate.

Should not give folic acid unless serum b12 is normal as folic acid can aggravate neuropathy. 5mg daily for 4 months, treat underlying cause

Pregnancy is the main cause. others include alcohol excess, liver disease, hypothyroidism ,haematological disorders, drugs (methotrexate, hydroxycarbamide, azathioprine)

Blood film will show macrocytic anaemia and increased reticulocytes. Will see normal b12, folic acid and lipid deposition in RBC membrane

will present and manage the same as hereditary spherocytosis except blood film will show eliptical shape RBCs

Intravascular haemolysis will have free haemoglobin binding to haptoglobin which when saturated, haemoglobin will then bind to albumin forming methaemalbumin (detected by Schumm’s test)

Free haemoglobin is excreted in the urine as haemoglobinuria / haemosiderinuria which is only seen in intravacular

mismatched blood transfusion, G6PD deficinecy, red cell fragmentation (heart valves, DIC, HUS), paroxysmal nocturnal haemoglobinuria, cold autoimmune haemolytic anaemia

haemoglobinopathies, hereditary spherocytosis, haemolytic disease of newborn, warm autoimmune haemolytic anaemia

can be divided into warm or cold types depending on at what temperature the antibodies best cause haemolysis. most commonly idiopathic.

you will see normocytic anaemia, reticulocytosis, low haptoglobin, raised LDH and bilirubin, spherocytes / reticulocytes, characterised by a +ve Coombs test

if the patients RBC or plasma has anti-RBC antibody = it will cause RBCs to be agglutinated when the anti-human globulin is added = +ve test

Direct is via adding patients RBCs, indirect is vai adding their plasma. Both cases contain antibodies to RBCs

usually igG mediated at high temperatures. Idiopathic mostly, can be caused by SLE or lymphomas.

Treat the underlying disorder, give prednisolone + / - rituximab is first line. blood transfusions and splenectomy are considered

usually igM mediated, works best at lower temperatures. agglutination results in the destruction of the RBC membrane as the immune system is activated against them. Will see raynauds or acrocyanosis. causes include lymphoma or EBV infections

formation of a fibrin mesh due to increased activation of the system of coagulation. This leads to shredding of the RBCs that flow through leading to schistocytes that can be observed in microscopy of blood film. Leads to unconjugated hyperbilirubinaemia

occurs in serious medical conditions like sepsis / maliganacy / trauma / complications during preganancy like HELLP syndrome (haemolysis, elevated LTFs, low platelets), where there is a release of pro-coagulants such as tissue factor. TF triggers extrinsic pathway and eventally the intrinsic pathway leading to widespread clot formation = ischaemia, necrosis, organ damage. Leads to clotting factors and platelets being heavily depleted = easy bleeding

Will see typical picture of prolonged PTT / APTT, bleeding time and platelet count / fibrinogen will be low

Treat underlying cause, supportive measures via ventilation / transfusion

Gene mutation that leads to lack of glycoprotein glycosyl-phophatidylinositol (GPI) = loss of proteins on surface of RBCs that inhibit complement cascade so complement is activated on RBCs now = haemolysis

will see red urine in the morning containing haemoglobin / haemosiderin. pancytopenia and increased risk of thombosis (lack of CD59 on platelet membranes = predispose to platelet aggregation)

Flow cytometry of blood to see low levels of CD 59 / 55 as gold standard now.

Management via eculizumab (monoclonal antibody against complement C5), BM transplant is curative

deficiency in ADAMTS13 which normally inactivitates large multimers of vWf and reduces platelet adhesion = less clot formation. Deficiency leads to abnoramlly large platelets to clump and form blood clots in small blood vessels, eventually leading to thrombocytopenia and can break up RBCs = haemolytic anaemia

Usually see thrombocytopenia, typically adult females, fever, microemboli causing fluctuating neuro signs.

treatment via haematologist involving plasma exchange, steroids, rituximab.