Haematology Flashcards
haematopoiesis (and lifespan of RBCs, plats, granulos)
turnover of cells is very quick:
Red blood cells have a lifecycle of about 120 days
Platelets have a lifecycle of about 7 days
Granulocytes have a lifecycle of only about 7 hours
pluripotent stem cells in the marrow (in fetus liver + spleen too, this is extramedullary); turns into a progenitor cell (common myeloid or lymphoid)
in presence of epo common myeloid progenitor cell -> basophilic erythroblast -> polychromatophilic erythroblast -> normoblast -> reticuocyte (enter circulation and mature over 24 hrs, losing final RNA and shrinking to become RBC; B12 and folate needed for protein (inc haem) synthesis
in presence of thrombopoietin common myeloid progenitor -> megakaryoblast -> megakaryocyte -> platelets
in presence of colony stimulating factor common myeloid progenitor becomes myeloblast; then M-CSF to monocytes, G-CSF to granulocytes, GM-CSF to grans + monos, multi-CSF to grans, monos, and down the plat and RBC pathways; common myeloid progenitor can also form mast cells directly; monocytes give rise to macros and dendritic cells; there are also lymphoid dendritic cells derived from common lymphoid progenitor
haematopoietic progenitor stem cell can also form common lymphoid progenitor, and from this NK cells or lymphocyte precursor then B cells -> plasma cells, else T cells
anemia causes
impaired production
- stem cells not differentiating or proliferating (aplastic anemia inc fanconi anemia, deficient EPO production in CKD)
-disturbance in maturation or prolif of erythroblasts (B12/folate def, anemia of prematurity, IDA, thalassemia, congenital dyserythropoietic anemia)
-otherwise impaired production (Myelodysplastic syndrome, anemia of chronic disease, displacement of marrow by tumour, fibrosis etc)
increased destruction
-haemolytic anemias
blood loss
-trauma, gynae loss, bleeding from malignancy in gut or bladder, hookworms whipworms schistosomes amoebiasis
-GI loss (ulcers, inflam, coeliac)
fluid overload
microcytic suggests production failure: IDA, thalassemia, sideroblastic think TAILS (thalassemia, anemia of chronic disease, IDA, lead poisoning, sideroblastic)
macrocytic incs megaloblastic if DNA synthesis impaired but RNA intact (b12/folate) whereas non-megaloblastic inc hypothyroid, liver disease inc alcohol, drugs that affect DNA replication like methotrexate, and consider multiple myeloma
normocytic usually acute blood loss, aplastic anemia, anemia of chronic disease, haemolytic, hypothyroid (AAAHH)
can also split normocytic into normal bone marrow (early IDA, CKD, chronic disease, hypothyroid, liver disease) or abnormal bone marrow (myelodysplasia, infiltration by leukaemia or myelofibrosis, hypoplastic/ aplastic anemia)
also consider haemorrhage and haemolysis
so microcytic do iron studies, fbc, U&Es, film, and if IDA confirmed then OGD + sigmoidoscopy; if not IDA then Hb electrophoresis esp if ethnic group incs risk of thalassemia
if normocytic U&Es, FBC and film, LFTs, TFTs, iron studies, LDH bili and haptoglobin (individually non-specific but in conjunction suggest haemolysis), B12 and folate, and consider DAT
if macrocytic then B12/folate, U&Es, TFTs, FBC and film, consider DAT, consider protein electrophoresis and myeloma screen, consider methylmalonic acid and homocysteine levels
further ix may inc abdo USS looking at spleen, and bone marrow trephine (if advised by haem)
also note mean cell haemoglobin concentration tells you if hypochromic or normochromic
anemia diagnostic algorithm
if pt is anemic calculate reticulocyte production index, is <2% follow path A and >2% follow path B
path A
look at MCV, if microcytic look at iron studies and if all consistent with IDA then that is diagnosis; if they aren’t then is mentzer index (MCV/RBC count) <13, if yes then do haemoglobin electrophoresis for thalassemias and other haemoglobinopathies; if no then is eGFR 60 or more? if yes then does pt have chronic disease/inflam/malig? if yes then is transferrin receptor-ferritin index >1.5? if no anemia of chronic disease, if yes anemia of chronic disease with IDA; if no to chronic disease presence then on film histo are there ringed sideroblasts? if yes then sideroblastic anemia, if no then other bone marrow failure; if eGFR <60 then look for hypochromia or low transferrin saturation and ferritin levels -> if not present then CKD anemia, if present then IDA + pt has CKD
if normocytic then look at eGFR, if <60 proceed as above; if 60 or more then is there chronic inflam/malig/disease? if yes then as above, if no then look at iron studies and B12/folate, may be early/combined anemia related to those, if those are normal then bone marrow trephine for hypo/aplasia or infiltration (leukaemia, tumour)
if macrocytic then check B12/folate, if either low that is cause and replace; if borderline check homocysteine and MMA and if either high suggests b12 deficiency; if not deficient in either then is pt on meds that can cause? if no then get a blood film with histo, if round macrocytes then check for alcohol, liver disease, thyroid disease, if none present then there is bone marrow failure
if histo shows oval macrocytes then bone marrow trephine for MDS, if negative then will be other bone marrow failure
pathway B for anemia algorithm
has pt been newly started on B12/folate/iron replacement? if yes suggests you’ve caught them at moment when treatment beginning to work but anaemia not yet resolved
if no, is haptoglobin low? (+LDH raised)? if no then anaemia is due to acute blood loss
if yes then haemolysis is confirmed: get blood film and check DAT; also get urine dip and microscopy to look for haemoglobinuria, to assess for risk of ATN
DAT positive then is IgG +ve and spherocytes in film? is so then warm haemolytic anemia; if instead CD3+ve and red cell agglutination on film then cold haemolytic anemia (and in babies consider blood group incompatibility)
if DAT negative then is mentzer index <13? is yes get haemoglobin electrophoresis for thalassemia, if no look at RBC morphology on film:
spherocytes can be due to burn injury, if no such injury present then check osmotic fragility test, if positive hereditary spherocytosis and proceed to genetic test, if no then if snakebite in history that is causing, if not then could be autoimmune as above or other rarer things
elliptocytes and stomatocytes should prompt genetic testing for their corresponding hereditary cytosis conditions
bite cells and heinz bodies: G6PD or enzyme in glutathione cycle (genetic testing)
sickle cells -> get Hb electrophoesis to confirm
if polychromasia induced by drugs or infection consider enzyme defect like PK deficiency, if no then is GPI ancho deficiency shown on flow cytometry? if yes then PNH, if no then liver/kidney disease or exercise induced haemolysis
unusual inclusions -> consider infection like malaria, bartonella
if basophillic stippling and lead levels raised then lead poisoning, if no then genetic enzyme problems
if schistocytes and helmet cells consider metal heart valves, microangiopathic haemolytic anaemia triggered by malignant hypertension, haemolysis related to vasculitis, or thrombotic microangiopathies (HUS, TTP, HELLP, DIC)
how many ml O2 in 100ml blood at diff sats (how many ml a 10% sats change is), hyperbaric O2 therapy, what paO2 and paCO2 should be, fundamental cause of normal and raised anion gap acidosis
100ml of blood binds 20.1ml of O2, as oxygen content of blood is 1.39 x hb conc x sats + dissolved (negligible); normal Hb conc is 15gHb per 100ml so fully saturated is 1.39 x 15
so sats of 90 contains 18.8ml, 80 is 16.6ml, 70 is 14.6ml etc (10% change is 2.1ml change)
dissolved oxygen is 0.003ml O2 per 100ml blood per mmHg paO2, so normally only 0.3mL O2 dissolved per 100ml so negligible
hyperbaric chamber for CO poisoning aims for 100-1000 paO2 which increases O2, up to max around 5ml per100ml blood aka 25% normal O2 delivery (plus some more as higher paO2 helps displace bound CO)
paO2 should be 10-13, paCO2 should be 4.7-6 - subtract 10 from fio2% to get predicted pao2
bicarb 22-28, BE -2-+2, anion gap10-18, lactate <2mmol/L
high base excess is metabolic alkalosis, low base excess is metabolic acidosis; raised anion gap is addition of acid eg DKA, normal anion gap is loss of bicarb eg diarrhoea, RTA
iron biochemistry (levels during day, transferrin saturation meaning, when transferrin reduced, best indicator of total body stores, zn protoporphyrin - 2 reasons higher)
normal adult serum level 10-40micromol/L, but can vary by 50% over 24hrs on circadian rhythm
transferrin saturation usually 30%, if falls to 20% or less then iron deficiency is likely
>50% suggests iron overload
transferrin/TIBC is increased in fe def anaemia and reduced during acute phase response, anemia of chronic disease, and during protein malnutrition
serum ferritin best indicator of total body stores and should be what you use to look for deficiency - conc normally >12microg/L, but increased in acute phase response so marginal deficiency cant be diagnosed off this in such states
zinc protoporphyrin expressed in micromol/ mol haem and usually <60, increases due to iron deficiency or lead exposure
anaemia (3 main sx, when get pallor and cardiac sx, 2 main ix needed, 3 main categories)
SOB on exertion, tiredness, headaches
if Hg <90g/L will have pallour of mucosal membranes plus raised CO (tachycardia and sometimes a systolic murmur)
must have FBC, stained blood film
macrocytic is MCV >98fl, normocytic 78-98, microcytic <78
also note platelets normally ravel on the outside of the flow of blood near the endothelium. When you’re anaemic the platelets are less close to the endothelium. This is why bring anaemic can increase your chance of bleeding. aka the brazil nut effect
anaemia of chronic disease (inc ix results, pathophys, mx, 5 conditions associated)
normo or micro, haemo >90g/L, serum fe and total fe binding capacity down, so TIBC and transferrin down, but ferritin normal or raised; crp usually raised
il6 -> liver -> hepcidin; hepcidin decs fe absorpt across gut, also causes macros to sequester iron; il1/6 tnf, inf-g also reduce erythropoises by altering stromal and progenitor cells response to epo
treat the disease, can give recombinant epo
seen in many malignancies, connective tissue disorders like SLE and RA, hypo/hyperthryoidism cause, acute and chronic renal disease, liver diseases
iron deficiency (3 common causes, 8 signs/sx, histo appearance, biochem picture, oral replacement inc s/e + how many mg a day, supplementing iron in infants when and why)
blood loss (inc heavy periods), malabsorption, insufficient intake (need more in pregnancy or menstruation)
as well as anaemia may get koilonychia, rigid brittle nails, angular stomatitis, glossitis, pica, hair thinning, pharyngeal web formation
hypochromic microcytic anaemia, poikilocytosis, anisocytosis, pencil cells, serum iron and ferritin low and transferrin (TIBC) raised
could test for blood loss (esp if not a menstruating age woman) inc urine dipstick, endoscopy
oral iron (ferrous sulphate) up to 3x daily before meals; other preparations inc ferrous fumarate (contains more iron), ferrous gluconate (less iron); can cause diarrhoea, constipation, nausea, abdo pain - you generally want 50-100(-200)mg elemental iron a day
note babies born with good iron stores, don’t use them up until 6mo -> from 6mo babies need iron supplement or foods/formula containing iron as breast milk alone doesn’t contain enough; after 1-2yo won’t need as long as theyre getting enough iron in their diet
investigating and treating iron def anaemia (how to confirm it, 6 things to check for in history, 4ix to consider, initial treatment (and what to do if not tolerated), why higher doses don’t work, how to monitor and what is an adequate response (+ what to do if inadequate), what to do after Hb and stores replenished, when to transfuse)
if suspect then confirm with iron studies
if IDA confirmed then you should assess in history for chronic overt blood loss (eg, nosebleeds, menstruation), blood donation, inadequate dietary intake, long-term NSAID or PPI usage and previous resectional or bypass surgery of the GI tract
you should do urinalysis and exclude coeliac disease; also do a FIT test to help determine whether 2ww; consider need for OGD and colonoscopy after risk assessment using verified tool
initial treatment of IDA should be with one tablet per day of ferrous sulphate, fumarate or gluconate. If not tolerated, a reduced dose of one tablet every other
day, alternative oral preparations or parenteral iron should be considered; aiming for 50-100mg elemental iron a day - higher or repeat doses ineffective as iron induces hepcidin release for next 24 hrs; if still not tolerated consider IV iron
patients should be monitored in the first 4 weeks for an Hb response to oral iron, and treatment should be continued for a period of around 3 months after normalisation of the Hb level, to ensure adequate repletion of the marrow iron stores; absence of an Hb rise of at least 10 g/L after 2 weeks of daily oral IRT (or 20g/L after 28 days) is strongly predictive of subsequent failure to achieve a sustained haematological response and should consider IV iron in these cases
After the restoration of Hb and iron stores with IRT, we recommend that the blood count should be monitored periodically (perhaps every 6 months initially) to detect recurrent IDA; if not restored after 3mo may need long term IRT
transfuse only if v anaemic (eg <70 Hb or <80 and cardio condition) + symptomatic
IV iron therapy - 6 contras, what else do you need to prescribe, requirement and how to split it, 5 times when to use Ganzoni formula
eg monofer
don’t give if: Known serious hypersensitivity to other parenteral iron products
* Non-iron deficiency anaemia (e.g. haemolytic anaemia)
* Iron overload or disturbances in utilisation of iron (e.g. haemochromatosis,
haemosiderosis)
* Decompensated liver disease
* First trimester of pregnancy
* Ongoing bacteraemia
can rarely cause hypersensitivity reactions so prescribe relevant PRNs
Determine patients cumulative iron need: generally if Hb >100 then 1g unless weight >70kg in which case 1.5g; 1.5g if Hb <100 unless >70kg in which case 2g
If the cumulative iron dose exceeds 20 mg iron/kg body weight, the dose must be split in two administrations with an interval of at least one week. It is recommended whenever possible to give 20 mg iron/kg body weight in the first administration
In patients who are likely to require individually adjusted dosing such as
patients with anorexia nervosa, cachexia, obesity, pregnancy or anaemia due to active bleeding the Ganzoni formula should be used
instead
sideroblastic anaemia
ringed sideroblasts on marrow biopsy - iron granules form ring around the nucleus
can be congenital, often an x linked (so mostly affects males) deficiency in haem synthesis
often acquired as part of a myelodysplasia in which case may see leucopenia and thrombocytopenia
megaloblastic anaemia (causes (7:6), 4 features, 4 test results, treatment inc order)
B12 deficiency (vegans, pernicious anaemia (autoimmune gastritis with raised serum gastrin and serum Ig to IF or gastric parietal cells), gastrectomy, bacterial colonization of SI, ileal resection or crohns disease (as absorbed bound to IF in ileum), sometimes h pylori infection), atrophic gastritis
folate deficiency (poor dietary intake (exacerbated by pregnancy or haemolytic anaemia, malignancy, severe chronic inflam like IBD, RA, psoriasis etc), malabsorption, folate can be remobed by dialysis as only loosely bound to serum protein
features: gradual onset anaemia, mild jaundice (ineffective erythropoises), glossitis and angular stomatitis, B12 only causes symmetrical peripheral neuropathy (pyramidal tracts and subacute combined degen of the cord)
macrocytic anaemia with hypersegmented neutrophils, raised serum bilirubin and LDH, serum B12 and folate will be disturbed
injections of B12 and oral treatment for folate, correct B12 first as treating folate at same time may precipitate a drop in B12 and thus peripheral neuropathy
haemolytic anaemia (common causes - inc 3 congen, 4 signs/sx, what can cause crisis, what you can get secondary, 5 test results)
many causes, some common ones: G6PD or PK deficiency, hereditary spherocytosis, secondary to SLE or eg certain infections eg malaria; prosthetic or stenosed heart valves can cause (esp if paravalvular leak after a graft which causes extra turbulence), DIC, haemolytic uraemic syndrome, mismatched transfusion
anaemia, jaundice, often splenomegaly and bone marrow expansion, parvovirus infection can precipitate aplastic crisis; can cause a folate deficiency anaemia secondary to the haemolysis
Hg normal or low, raised reticulocytes, altered red cell shape on blood film; low haptoglobin if intravascular haemolysis; unconj bili up
microcytic anaemia (inc 5 sideroblast causes), 5 causes of normocytic anaemia
helpful mnemonic for understanding the causes of microcytic anaemia is TAILS.
T – Thalassaemia
A – Anaemia of chronic disease
I – Iron deficiency anaemia
L – Lead poisoning
S – Sideroblastic anaemia (congen, copper or B6 def, lead poisoning, zinc overdose, alcohol)
Normocytic Anaemia Causes
There are 3 As and 2 Hs for normocytic anaemia:
A – Acute blood loss
A – Anaemia of Chronic Disease
A – Aplastic Anaemia
H – Haemolytic Anaemia
H – Hypothyroidism
macrocytic anaemia (megalo + 5 other causes)
can be megaloblastic or normoblastic. Megaloblastic anaemia is the result of impaired DNA synthesis preventing the cell
from dividing normally. Rather than dividing it keeps growing into a larger, abnormal cell. This is caused by a vitamin deficiency.
Megaloblastic anaemia is caused by:
B12 deficiency
Folate deficiency
Normoblastic macrocytic anaemia is caused by:
Alcohol
Reticulocytosis (usually from haemolytic anaemia or blood loss)
Hypothyroidism
Liver disease
Drugs such as azathioprine
Myelodysplastic syndrome
pernicious anaemia - invest, treatments
Intrinsic factor antibody is the first line investigation
Gastric parietal cell antibody can also be tested but is less helpful
treated with 1mg of intramuscular hydroxycobalamin 3 times weekly for 2 weeks, then every 3 months
autoimmune haemolytic anaemia management (4 things)
Blood transfusions
Prednisolone (steroids)
Rituximab (a monoclonal antibody against B cells)
Splenectomy
B12 def (9) and folate def (8) causes; microcytic but not iron def what could it be?
B12 def - vegans, pernicious, gastrectomy, atrophic gastritis, H pylori, ileal resection (crohns), SIBO, malnut; oval macrocytosis on histo
folate - dietary, coeliac/malabsorb, alcohol, liver disease, anticonvulsants, malignancy, inflam conditions, haemolytic anaemia
microcytic but not iron deficient (maybe accumulating iron) could be thalassaemia
nitric oxide misuse (acute sx, chronic sx and pathophys inc the 2 things you dont make, sx, 3x ix, when admit, mx)
Acute exposure results in short-lived and reversible CNS effects including euphoria and sedation
Chronic N2O exposure results in dose-dependent inactivation of vitamin B12 - leading to demyelination and possible myelosuppression; inactivation as it oxidises the cobalt atom in vit B12, so B12 is not available as a coenzyme to convert homocysteine to methionine (increasing the homocysteine level) or methylmalonyl-CoA to succinyl-CoA (increasing the MMA level). This interrupts methylation of myelin proteins, leading to instability of myelin sheaths and axonal loss
find sensory problems, sensory ataxia, dorsal column dysfunction, reduced limb power, reduced reflexes
may see macrocytic anaemia and bone marrow suppression; low B12 levels; demyelination on MRI - symmetrical T2 hyperintensities
admit if can’t walk or has neuro/haem sx
B12 1mg daily for 2 weeks then weekly for 4 weeks then monthly until recovered
haemolytic anaemia subdivisions (causes for each 7:11), biochem markers for each (3 same and 1 diff, how 2 of the same actually may differ)
either intravasc or extravasc; intra: DIC, TTP-HUS, HELLP, transfusion reaction, PNH, prosthetic valves;
extra inc autoimmune (warm (SLE,CLL, HL) or cold (mycoplasma etc)), intrinsic RBC defects (membrane defects, enzyme deficiencies, haemoglobinopathies),
malaria, wilsons, hypersplenism (eg portal hypertension), lead poisoning
both have decreased haptoglobin and increased LDH and unconj bili, but with extravasc haemoglobin doesnt escape into blood so no haemogloninaemia/uria
LDH may be up much higher in intravasc, and small amount of haemoglobinaemia/uria possible for extra; hapto may be even lower in intr than extr
ABO and Rh typing - forward and reverse grouping, crossmatch, DAT and indirect Coombs
reagents containing antibodies against the A, B, and RhD antigens are added to suspensions of blood cells. If the
relevant antigen is present, the antibodies in the reagent will cause the red blood cells to agglutinate (clump together), which can be
identified visually
In addition to identifying the ABO antigens, which is termed forward grouping, routine ABO blood typing also includes identification of
the ABO antibodies in the person’s plasma. This is called reverse grouping; person’s plasma is added to type A1 and type B red blood cells.
The plasma should agglutinate the cells that express antigens that the person lacks
prior to receiving a blood transfusion, individuals are screened for the presence of antibodies against antigens of non-ABO blood group
systems
Crossmatching, which is routinely performed before a blood transfusion, involves adding the recipient’s blood plasma to a sample of the
donor’s red blood cells. If the blood is incompatible, the antibodies in the recipient’s plasma will bind to antigens on the donor red
blood cells
direct Coombs test detects antibodies that are stuck to the surface of the red blood cells
used to test for autoimmune hemolytic anemia
blood sample is taken and the red blood cells are washed (removing the patient’s own plasma and unbound antibodies from the red blood cells
and then incubated with anti-human globulin (“Coombs reagent”). If the red cells then agglutinate, the direct Coombs test is positive
indirect Coombs test is used in prenatal testing of pregnant women and in testing prior to a blood transfusion. The test detects
antibodies against foreign red blood cells. In this case, serum is extracted from a blood sample taken from the patient. The serum is
incubated with foreign red blood cells of known antigenicity. Finally, anti-human globulin is added. If agglutination occurs, the indirect
Coombs test is positive
haematogenesis (+ life span of RBC)
long term HSC to short term HSC, which can become common lymphoid progenitor or common myeloid progenitor; latter can become granulocyte macrophage progenitor GMP, then baso/eosino/neutrophil+macro precursors, or megakaryocyte/erythrocyte progenitor MEP, then megakaryocyte or erythroid progenitor, last one then becoming RBC and being called erythroblasts (still nucleated) and reticulocytes (immature RBC which no longer has nucleus); RBCs typically live 120 days then are destroyed in spleen;
paeds haematology physiology (where Hb production starts, when/how it switches x2,, physiological anaemia dates and causes, subunits in HbA and HbF and ratio in average child and at birth)
Hb production by 3rd week gestation, mostly in yolk sac
by month 3-4 liver takes over, and then by mo 6-7 bone marrow; at birth haematopoieses in all bones, reducing to mostly vert/ribs/sternum/pelvis as kid ages
neonates relatively polycythaemic, falls to lowest level (physiological anaemia) by 2-3mo, then rises
HbF (2a2g), by birth HbA (2a2b) is 20% with HbF the rest; HbF dissociation curve is to the left, ie v high affinity for O2
average child has 95% HbA, 2% HbF, 2% HbA2
physiological anaemia as great inc in paO2 at birth suppresses epo production for several weeks which then triggers more epo production as Hb reduces
reticulocytes (what it causes, 3 reasons for low, 4 reasons for high)
causes polychromasia
if low number of retics and anaemic means bone marrow abnormal, or v shortly after episode causing acute anaemia so no time to respond, or retics being destroyed
high levels in haem anaem, acute severe bleed, remission of aplasia beginning, response to treatment of haematinic def
rouleaux
rows of stacked RBCs, caused by inflam or malig
dimorphic blood film 3 causes
combo fe and B12/folate def
fe def and had blood transfusion
sideroblastic anaemia
autoimmune haemolytic anaemia - general ix result, 2 things make warm type more likely (why), 7 causes of warm, 4 mx things; how to tell cold (and why), 4 causes, relative amount of haemolysis, 3 treatments, what is no use; PCH
normochromic w pos coombs
IgG coating, spherocytosis make warm antibody more likely (IgG pref agglut >37deg)
this form idiopathic 60% of the time, also underlying autoimmune disorders like RA, SLE, lymphoma, CLL, levo/methyldopa, penicillin
steroids treat, if no improvement then eg azathioprine; if chronic splenectomy; avoid transfusions
cold type is IgM (pref agglut <37deg), usually following mycoplasma or inf mono but also in SLE and some lymphomas; haemolysis tends to be milder
avoid cold, immunsup, warm transfusion; splenectomy no use
paroxysmal cold haemoglobinuria associate with congen/acquired syphilis but also after viral gastroent, chickenpox, mumps, flu, adenovirus; IgG binds red cells in cooler parts of body and complement lyses in warmer parts
evans syndrome
rare autoimmune condition that presents with two or more cytopaenias, which commonly include warm autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenia (ITP), with or without immune neutropenia
usually considered a disease of children and cause is unknown
ruling out common etiologies such as cold agglutinin disease, thrombotic thrombocytopenic purpura (TTP) through careful evaluation of the peripheral blood smear, infectious causes (such as HIV, Hepatitis C), other autoimmune conditions and malignancies are required before the diagnosis of Evans syndrome can be made
transfusion, steroids, IVIg
Rituximab or splenectomy may be considered in those refractory to the standard treatment
G6PD inheritance, path/mx
inherited x linked recessive
hexose monophos pathway (aka pentose phosphate pathway) produces reducing power for cell in form of NADPH
this maintains glutathione in reduced state, G6PD absence thus means less reduced glutathione so cross-linking of spectrin (incg rbc rigidity) and haem oxy to methaem giving heinz body precip; both effects lead to haemolysis
assay for g6pd enzyme is diagnostic; repeat if normal but in crisis as retic production and haem of mature cells can give false neg
treat infection/remove drug trigger, blood transfusion; splenectomy usually no use (unlike hered spher)
pyruvate kinase def secon most common, inherited AR, also exacerbate by stress/infection
tell ABO incompatibility from rh incomp (chromosome location, timing, 2 ix, which is milder)
ABO is cr9, rh is cr1
rh doesnt happen in first preg, ABO can
direct coombs neg or weakly pos for ABO and strongly pos for rh
blood film shows microspherocytes and reticulocytosis for ABO, only latter for rh
ABO haemolysis usually milder than rh
sites of absorption for fe, B12, folate; how long B12 and folate stores last; causes in kids (fe 3, B12 3, folate 1 rare 2 common), 4 things caused by B12/folate def
fe protonated in stomach then absorbed in duodenum and jejunum; B12 combined with IF in stomach (made by parietal cells) then absorbed in terminal ileum, folate absorbed unchanged in duodenum and jejunum
B12 stores last 3-4 years, folate stores last 3-4 months
causes: fe bleeds esp GI, inadequate intake (premie infants may get at 6-12mo, also see in bottle fed babies, late weaning etc), malabsorption; B12 inadequate intake (vegan), malabsorption (inc pernicious anaemia); folate reduced intake rare in kids, inc’d utilisation eg pregnancy/chronic haem anaem, antifolate drugs (phenytoin, methotrxate)
B12 and folate def cause macro anaemia, hyperseg neutrophils, leucopenia (so more infections), thrombocytopenia (bleeding tendency); B12 also neuro signs
schilling test
saturate storage sites with B12 im injection, then oral radiolabelled B12 -> will be secreted in urine as storage sites full, so collect urine for 24hrs and should see 10-30% secreted; reduced excretion means reduced absorption
then give same labelled B12 but w intrinsic factor, if excretion improves then if production problem and if no increase then ileal problem
4 sources of lab biochem errors and what they look like
blood kept for long time before sending to lab - K, phos, AST up as leak through RBC membrane
blood haemolysed after diff venesection - raised K, phos, AST
prolonged venous stasis during venesection - high plasma Ca, protein fractions, T4, K, phos due to inc’d hydrostatic pressures forcing fluid/electrolytes out of vasc compartment but leaving larger molecules like proteins and ions bound to those
taking blood from arm with infusion running into it - all concs more dilute and glucose, Na, K may mirror what is in infusion fluid
physiologic anaemia of infancy
Physiologic anaemia of infancy causes most cases of anaemia in infancy
- a normal dip in haemoglobin around six to nine weeks of age in healthy term babies. High oxygen delivery to the tissues caused by the high
haemoglobin levels at birth cause negative feedback. Production of erythropoietin by the kidneys is suppressed and subsequently there is reduced production of haemoglobin by the bone marrow.
G6PD def (inheritance inc 3 common ethnicities, 3 triggers, what you see on the film, diagnosis, 6 causes for one of the 3 triggers)
more common in Mediterranean, Middle Eastern and African patients. It is inherited in an X linked recessive pattern, meaning it usually affects males, as they have only a single copy of the gene on their single X chromosome.
It causes crises that are triggered by infections, medications or fava beans (broad beans). Can get gallstones
Heinz bodies may be seen on a on blood film. Heinz bodies are blobs of denatured haemoglobin (“inclusions”) seen within the red blood cells
Diagnosis can be made by doing a G6PD enzyme assay
Medications that trigger haemolysis and should be avoided include:
Primaquine (an antimalarial)
Ciprofloxacin
Nitrofurantoin
Trimethoprim
Sulfonylureas (e.g gliclazide)
Sulfasalazine and other sulphonamides
hereditary spherocytosis, when to suspect (4 things in classic pt), genetic pattern, what is often in history, dx, acute presentation form, possible other complication
caucasian child w negative coombs test but haem anaem and splenomeg
AD, splenomeg absent in 20% cases
half cases have history of neonatal jaundice
diagnose from film
may present in aplastic crisis if infected w erythrovirus B19 (aka parvovirus B19), just like sickle cell
if said child devs abdo pain (poss rec) consider pigment gallstones (biliary colic, maybe cholecystitis) - uss will confirm
Hb electrophoresis - general appearance of bands, what you see in sickle cell (+trait), sickle cell beta+thal, sickle cell B0 thal, sickle SC, B thal major, B thal minor; when to consider A thal and how to diagnose it
bands labelled with Hb type, width corresponds to proportion of that type
sickle cell: no HbA, high HbF (10%), vast majority HbS
sickle cell trait: mix of HbS and HbA w no HbF
Sickle cell beta+thal variant is some of HbS/A/F/A2, sickle bell B0 thal is HbS/F/A2; sickle SC disease 50:50 HbS/HbC
in sickle cell MCV is normal so if lots of HbS + microcytic consider a thal variant as above
B thal major is HbF 90%, some HbA2
b thal minor is 4-7%HbA2, 1-3% HbF, rest HbA
if microcytic anaemia w normal iron studies and Hb electrophoresis then consider a thal, diagnosed by specific genetic tests
alpha thalassaemia (just the 4 gene possibilities and results of each)
all 4 inactive gives hydrops foetalis, in utero death; 3 inactive gives HbH disease with marked microcytic hypochromic anaemia Hb 60-110 with splenomegaly
a thalassaemia trait if 1-2 inactive gives microcytic hypochromic red cells, raised red cell count; if 2 deleted may get mild anaemia
beta thalassaemia (inc cause, sx, 3 types mx)
major if inherit from each parent a deficient B causing excess A chains; anaemia starting from 3-6mo (up to 4yr if mild) with mild jaundice, pallor, failure to thrive; organomegaly; hypochromic, microcytic, severe anaemia Hg 20-60 g/L; needs regular transfusion; iron chelation therapy with desferrioxamine
thalassaemia intermedia: milder with less severe anaemia needing few or no transfusions
beta thalassaemia trait: mild microcyctic anaemia, raised red cell count, raised Hb a2 level
sickle cell disease (aa path, 4 triggers of crisis, 6 places it can precipitate + effect, cause of aplastic crisis, 2x concurrent problems, 5 things you can get chronically, why anaemia sx usually mild, 4 vaccines, 2 meds you might need to take)
valine sub for glutamic acid in beta chain, so insoluble in deoxy state and crystallises
like other chronic haemolytic anaemia but with crises: infection, dehydration, acidosis, deoxygenation
deposits of sickled cells can cause ischaemia and infarction giving abdo pain, pain in back/pelvis/ribs/long bones (or fingers - dactylitis), in CNS giving a stroke or fits, in lungs (acute chest syndrome), spleen, kidneys
B19 parvovirus gives aplastic crisis which is okay in healthy people but if reduced rbc survival due to eg sickle cell you get rapid acute severe anaemia needing a blood transfusion; inc’d utilization can lead to concurrent folate deficiency anaemia
splenic function reduced so inc’d susceptibility to pneumococcal infections (pneumonia, menigitis) plus other types
may get avascular necrosis of bones, chronic leg ulcers, pulmonary hypertension, cardiomyopathy, renal pap necrosis (inc’d risk of dehydration alongside polyuria)
Hb is 70-90 but anaemia symptoms usually mild as Hb-S O2 dis curve shifted to right; blood film will show sickle cells
pneumococcal, H influenzae, flu, meningococcal vaccines, folate, if splenic atrophy then oral penicillin indefinitely
thalassaemia (effect on spleen and bone, diagnosis and how you get iron overload (3 reasons, what it looks like, monitoring and 2x treatment strats), types and management inc what Cr alpha globin gene on, 5x mx for alpha thal)
red blood cells are more fragile and break down more easily. The spleen acts as a sieve to filter the blood and remove older blood cells. In thalassaemia the spleen collects all the destroyed red blood cells and swells, resulting in splenomegaly.
The bone marrow expands to produce extra red blood cells to compensate for the chronic anaemia. This causes a susceptibility to fractures and prominent features such as a pronounced forehead and malar eminences (cheekbones).
Haemoglobin electrophoresis is used to diagnose globin abnormalities.
DNA testing can be used to look for the genetic abnormality
Iron overload occurs in thalassaemia as a result of faulty creation of red blood cells, recurrent transfusions and increased absorption of iron in response to the anaemia.
Patients with thalassaemia have serum ferritin levels monitored to check for iron overload. Management involves limiting transfusions and iron chelation.
Iron overload in thalassaemia causes effects similar to haemochromatosis
Alpha-thalassaemia is caused by defects in alpha-globin chains. The gene coding for this protein is on chromosome 16. 1 chain defect silent carrier, 2 chain defect a thal trait minor and dont need treatment, 3 chain defect HbH disease symptoms and needs treatment 4 copies Barts hydrops fatal
Management:
Monitoring the full blood count
Monitoring for complications
Blood transfusions
Splenectomy may be performed
Bone marrow transplant can be curative
Beta thalassaemia minor causes a mild microcytic anaemia and usually patients only require monitoring
beta thalassaemia intermedia have two abnormal copies of the beta-globin gene. This can be either two defective genes or one defective gene and one deletion gene.
Thalassaemia intermedica causes a more significant microcytic anaemia and patients require monitoring and occasional blood transfusions.
If they need more transfusions they may require iron chelation eg desferrioxamine
beta thalassaemia major are homozygous for the deletion genes. They have no functioning beta-globin genes at all. This is the most severe form and usually presents with severe anaemia and failure to thrive in early childhood.
Thalassaemia major causes:
Severe microcytic anaemia
Splenomegaly
Bone deformities
Management involves regular transfusions, iron chelation and splenectomy. Bone marrow transplant can potentially be curative.
abdo pain + anaemia (7)
sickle cell disease, lead poisoning, G6PD, bleeding GI, vasculitis eg HSP, chronic GI disease eg crohns, pigmented gallstones
sickle cell pathology; sideroblastic anaemia appearance and causes
sickle pathology: polar amino acid glutamate is substituted by non-polar valine in each of the two beta chains (codon 6). This decreases
the water solubility of deoxy-Hb in the deoxygenated state the HbS molecules polymerise and cause RBCs to sickle
sickle cells are fragile and haemolyse; they block small blood vessels and cause infarction
sideroblastic anaemia: a microcytic anaemia w/o iron def, w basophilic stippling, ringed sideroblasts; congen, or alcohol/lead/TB meds
sickle cell (investigation, 10 symptoms/complications, long term management - 6 things)
mutation in beta chain
have an abnormal variant called haemoglobin S (HbS) - shows on Hb variant screen (electrophoresis)
Anaemia
Increased risk of infection
Stroke
Avascular necrosis in large joints such as the hip
Pulmonary hypertension
Painful and persistent penile erection (priapism)
Chronic kidney disease - esp left kidney, may have pap necrosis, renal infarction
Retinopathy
Sickle cell crises
Acute chest syndrome
Avoid dehydration and other triggers of crises
Ensure vaccines are up to date
Antibiotic prophylaxis to protect against infection with penicillin V (phenoxymethypenicillin) in vulnerable pts
- at risk of encapsulated organisms due to hyposplenism
Hydroxycarbamide can be used to stimulate production of fetal haemoglobin (HbF). Fetal haemoglobin does not lead to sickling of red blood cells. This has a protective effect against sickle cell crises and acute chest syndrome.
Exchange transfusion for severe anaemia
Bone marrow allograft from siblings can be curative
sickle cell crises (4 types inc cause, sx, mx)
Vaso-occlusive crisis is caused by the sickle shaped blood cells clogging capillaries causing distal ischaemia. It is associated with dehydration and raised haematocrit. Symptoms are typically pain, fever and those of the triggering infection; keep O2 sats >94%, keep hydrated, give adequate analgesia (may need PCA morphine)
Splenic sequestration crisis is caused by red blood cells blocking blood flow within the spleen. This causes an acutely enlarged and painful spleen. The pooling of blood in the spleen can lead to a severe anaemia and circulatory collapse (hypovolaemic shock).
Splenic sequestration crisis is considered an emergency. Management is supportive with blood transfusions and fluid resuscitation to treat anaemia and shock. Splenectomy prevents sequestration crisis and is often used in cases of recurrent crises
Aplastic crisis describes a situation where there is a temporary loss of the creation of new blood cells. This is most commonly triggered by infection with parvovirus B19
diagnosis of acute chest syndrome requires:
Fever or respiratory symptoms with
New infiltrates seen on a chest xray
This can be due to infection (e.g. pneumonia or bronchiolitis) or non-infective causes (e.g. pulmonary vaso-occlusion or fat emboli).
Is a medical emergency with a high mortality and requires prompt supportive management and treatment of the underlying cause:
Antibiotics or antivirals for infections
Blood transfusions for anaemia
NIV/ventilation
beta thal trait vs fe def anemia - besides haematinics and Hb electrophoresis, 3 other diffs
beta thal has disprop low MCV (50-60 usually), red cell count usually raised in b thal and lower in fe def, RDW v high in fe def but normal in beta thal; Hb electrophoresis to confirm if unsure
diamond-blackfan syndrome (4 signs, what the anamia is like and retic count + HbF, what bone marrow biopsy shows, 3x mx), transient erythroblastopenia of infancy
pure red cell aplasia 90% present before 1yo, generally congen
may see short stature, web neck, cleft lip, triphalangeal thumb (or other physical dev problems)
anaemia is normo/macrocytic w low retics, HbF will be elevated; bone marrow will show absent rbc precursors
steroids, if insufficient response then regular transfusions; bone marrow transplant in some
also transient erythroblastopenia of infancy is similar but self limiting, presents a bit later, no HbF and normal phenotype, will be preceded by viral illness
19 ways in which sickle cell anaem can present
chronic haem anaemia
hand/foot syndrome - usually toddles, recu pain + swelling oft w fever
bone pain/dactylitis
chest pain (may be pleuritic)
priapism
renal pap necrosis (loss of conc ability so polyuria/enuresis, long term CKD)
abdo pain (spleen/liver may infarct or may be pigment gallstones)
infection (oft encapsulated)
osteomyelitis
chronic leg ulcers
CVA (hemiplegia, cranial nerve palsies)
pulmonary HTN
splenic sequestration syndrome
aseptic necrosis of fem head
growth problems/delayed puberty
acute chest syndrome
aplastic crisis (oft provoked by erythrovirus B19 and lasting 2-3 weeks)
heart failure - cardiomyopathy, pulm HTN
blindness sec to retinal infarction/detachment
2 ix for diagnosis; 5 mx for acute sickle cell; exchange transfusion 2 reasons for and 6 problems of this; 6 chronic mx
ix: blood film, Hb electrophoresis
mx: fluids, analgesics - may need PCA, O2 keep sats >94%, abx empirically; transfusions in limited cases
exchange transfusion with life threatening acute chest syndrome or CVA; note stored blood 2,3DPG levels low which means reduced O2 delivering capacity; also risks of exchange transfusion inc hyperkal, hypocalc, hypotherm, heart failure, acidosis
chronic mx: folate, penicillinV proph, pneumo vax after 2yo, parental education (keep child well hydrated, recognise crises etc), genetic counselling, possibly bone marrow transplant
sickle cell paeds general mx in CAU
unusual now to make a new diagnosis of major haemoglobinopathy such as SCD in
anyone other than a child who was not part of the screening programme eg. born abroad or much older child. Haemoglobinopathy screening should be considered when the child’s status is not known, when they present with features of SCD, prior to an operation or if the
appearance of their blood count suggests a haemoglobinopathy
Criteria for Admission
* Agonising pain (ie. unresponsive to analgesics at home/ requiring opiates)
* Increased pallor, breathlessness or exhaustion
* Marked pyrexia > 38.5 o
C (especially when with signs of sepsis)
* Chest pain (especially when with signs of lung consolidation)
* Abdominal pain or distension (including diarrhoea or vomiting)
* Sequestration
* Severe thoracic / back pain
* Headache, drowsiness, CVA, TIA or any abnormal CNS signs
* Priapism (> 2 hours)
Blood tests may be avoided if all the following criteria are fulfilled -
* A simple painful (VOC) crisis
* Blood tests done in the hospital in the last 12 months
* Non febrile
* Not hypoxic (SaO2 = clinic values)
* No signs of infection
* Looks well
However if the child does not fulfil these criteria, then perform the following tests:
* Full blood count (FBC) and reticulocytes (retics)
* Group and save and antibody screen
* Haemoglobin (Hb) electrophoresis (measures % HbS / F / A) only if
- recently transfused
- if Hb F% levels not known
* Urea and electrolytes (U+Es)
* Creatinine
* Liver Function Test (LFTs)
* Bone profile
* C-reactive protein (CRP)
* Urine dipstick and MC&S
culture as appropriate, CXR if chest sx, CTH if stroke sx, consider ABG if SpO2 <90%, atypical pneumonia screen depending on CXR, abdo USS if gallstones or spleen problem, serology for Parvovirus B19 IgM if fall in Hb with low retics
ECG if cardiac pain
Amylase if abdo sx
Screen stool for Yersinia and serum for Yersinia antibodies if patient on desferrioaxamine
X-rays of bones and joints show little or no change in the first week of an acute illness
and rarely differentiate between infarction and infection. Ultrasound should be
considered for suspected osteomyelitis, MRI also has a role. X-rays can be useful in
confirming avascular necrosis as a cause of joint / referred pain
aim of treatment is to break the vicious ‘sickling‘ cycle
->hypoxia & acidosis -> more sickling -> all of which are exacerbated by dehydration
* This is best achieved by:
a. Hydration
b. Oxygenation
c. Prompt and adequate analgesia (pain relief)
d. Early and prompt treatment of infection
e. Identification and treatment of any complications
assess for dehydration, strict fluid I/O and hyper-hydration, with 1.5 litres / m2
/ day - PO where possible, IV if severe pain or abdo sx (careful also not to overload pt)
Blood U+Es and creatinine should be regularly monitored
Note that a slightly raised urea is significant, as these children normally have a low blood urea
Give O2 aiming SpO2 >95% if desat while SVIA or any chest/abdo sx
Patients who are admitted with uncomplicated painful VOC without specific evidence of infection should continue Penicillin V prophylaxis - if infection suspected stop it and start ceftriaxone (co-amox PO alternative), with azithromycin if any chest signs or abnormal CXR
Venous Thrombo Embolism (VTE) prophlylaxis is recommended in all children who are pubertal or over 11 years of age.
If there are no indications for admission, can be discharged with:
* A supply of oral analgesia
* Instructions to drink 1.5L / m2 / day
Mild pain gets PO paracetamol, if moderate (pain score 2) or didn’t respond then regular ibuprofen or diclofenac and if >12yo codeine/dihydrocodeine; if pain still not controlled or pain score 3 then above measures + STAT intranasal diamorphine 100mcg/kg and STAT oramorph 400mcg/kg, reassess after 30min to 1hr: rpt opioid if still in pain otherwise continue managing as moderate but with PRN oramorph, reassess after another 30-60 mins and can give one more oramorph if no resp depression but also need to contact pain team and set up PCA at this point or if <6yo consider opioid infusion; PCA fentanyl a later stage option
sickle cell paeds - initial presentation and long term mx
New patients seen for full history and initial assessment by a consultant with sickle cell knowledge
On initial presentation they must be prescribed PenV and folic acid and take both regularly
Well children with SCD are seen 3-6 monthly until 2 years of age and 6 monthly until their
5th birthday and annually thereafter
It is essential that all children with sickle cell disease take penicillin twice daily continuously (or clarithromycin, if penicillin allergic), starting by the age of 3 months
Children should be vaccinated as per the UK vaccination schedule; Pneumovax is given to children with sickle cell disease over the age of two years and five yearly thereafter, for life
Chelation therapy should commence after a child has received 15-20 transfusions or
when the ferritin reaches >1000 µg/l; Desferrioxamine is the chelator of choice. Desferrioxamine has a detrimental effect on
skeletal growth so treatment should be deferred until the age of 2 unless iron overload is particularly severe; Abdominal pain or diarrhoea may indicate infection with Yersinia (stop Desfer, admit, discuss with microbiology consultant)
Hydroxyurea if:
Patients with repeated severe pain episodes ( > 3 admissions to hospital per year).
Frequent severe pain episodes managed at home ( sufficient severity to interfere with
school and quality of life)
More than two chest crises or one chest syndrome requiring ventilatory support (PICU
admission)
Severe symptomatic anaemia
It:
Increases in MCV & RBC water content reducing the sickling process.
Increases HbF levels and reticulocytes
Increases the haemoglobin level by 10-20 g/L
Reduces inflammation
Needs FBC check every 2 weeks for the first 2 months or after dose increase, then every 8
weeks thereafter
sickle cell paeds managing specific complications
Reassurance - give the patient the assurance that their pain will be relieved
as soon as possible
Distraction
* Heat pads / warmth
* Establishing a position of maximum comfort
limb/joint pain usually due to VOC crisis but the possibility of osteomyelitis or septic
arthritis needs to be considered (If febrile, start IV antibiotics (Ceftriaxone) after cultures taken making sure to discuss with onc call consultant before aspirating joint, if temperature fails to respond to antibiotics after 48-72hrs repeat blood cultures, ESR, CRP, and consider ultrasound scan or MRI)
abdo problems may inc constipation (common esp if having opioids), abdominal crisis characterised by abdominal distension, generalised abdominal
tenderness but no rebound tenderness and diminished bowel sounds, and girdle syndrome haracterised by an established ileus, with vomiting, a silent distended abdomen and distended bowel loops and fluid levels on abdominal x-ray - this latter group may need NBM, NGT, IVF; Girdle syndrome is an indication for exchange transfusion; also consider all usual causes of abdo pain and start incentive spirometry
chest syndrome:
Care should be taken with opiate administration in any type of crisis, as over sedation may result in hypoventilation, atelectasis and worsening hypoxia precipitating a chest crisis
Needs urgent senior r/v, O2 +/- high flow or CPAP, analgesia, incentive spirometry, abx, continuous SpO2 monitoring in HDU, may need transfusion or even exchange trans
stroke needs urgent exchange transfusion
acute intermittent porphyria
autosomal dominant disorder of heme biosynthesis due to mutations in the porphobilinogen deaminase gene
predisposes heterozygous patients to life-threatening acute neurovisceral attacks that are precipitated by various factors, including porphyrinogenic drugs (e.g., P450 inducers), alcohol, infection (eg preceding resp infection or fever), stress, prolonged fasting and chronic under nutrition, and steroid hormones. These factors induce the synthesis of aminolevulinic acid synthase 1 (ALAS1), the first and rate-limiting enzyme in the heme biosynthetic pathway. When hepatic ALAS1 is induced, the partial PD enzyme deficiency becomes limiting, resulting in the marked accumulation of the neurotoxic porphyrin precursors, aminolevulinic acid (ALA), and porphobilinogen (PBG)
most common clinical presentation of an acute porphyric attack is severe abdominal pain, accompanied by vomiting, constipation, and abdominal distention, which can masquerade as an acute abdomen. Behavioural changes such as irritability, insomnia, emotional lability and hypertension and tachycardia due to sympathetic over-activity are important clues for the diagnosis; hyponatremia often occurs during severe attacks (SIADH picture) and can lead to seizures or an altered sensorium or even coma. The acute onset of progressive limb weakness due to motor axonopathy accompanied by myalgia can be extremely debilitating for patients. If these symptoms are not recognized and treated early, they can lead to residual morbidity and mortality due to bulbar and respiratory muscle paralysis
attacks classically present with dark-red photosensitive urine
Physical examination is usually unremarkable initially, later reduced tendon reflexes and weakness are present, and patients may lie in the foetal position in response to extreme pain and debility
urinalysis shows elevated urine porphobilinogen which confirms diagnosis of AIP, hereditary coproporphyria (HCP), or variegate porphyria (VP). A positive test should be indicated with an increase of five times normal, not just a slight increase which can occur with dehydration. To distinguish between AIP from HCP and VP, fecal porphyrin levels are normal in AIP but elevated in HCP and VP
discontinue trigger, give dextrose infusion, haematin treats the attack itself, opioids +/- neuropathic analgesia eg gabapentin; seizures may end with BZDs, and be careful which AED used if started as many induce CYP and so can trigger/exacerbate attack
Elevation of aminolevulinic acid from lead-induced disruption of heme synthesis results in lead poisoning having symptoms similar to acute porphyria so this is a ddx
major haemorrhage (what is the primary important parameter that falls, what is its proxy, when bp changes, 3 things that prevent compensation, where to look for bleeding, what to give, interpreting thromboelastogram, 3x definitions for major haem)
blood loss -> msfp down (“underfilled”), so VR and CO down
central venous pressure is proxy for msfp
can lose 15-20% of blood volume w/o seeing BP change (unless eg old, on beta blockers or have autonomic dysfunction etc so system cant compensate for hypovolaemia)
blood on the floor and 3 more (thorax, abdo/pelvis, long bones)
acute coagulopathy of trauma shock due to hyperfibrinolysis (so give tranexamic acid 1g after compression/tourniquets/splints etc)
giving fluids alone is futile -> ongoing haemorrhage needs surgical control fast
in resus room: massive transfusion protocol (immediate oneg prc/ffp via rapid transfuser 1:1 ratio) and 1g tranexamic acid infusion over 8 hours; whole body CT to find bleeding (exploratory lap if not stable enough)
flat bit of thromboelastogram is coag factors; then like sideways wide glass, hypercoaguable if wide glass; long stem and narrow glass is hypocoagulable
Major haemorrhage is variously defined as:
Loss of more than one blood volume within 24 hours (around 70 mL/kg, >5 litres in a 70 kg adult)
50% of total blood volume lost in less than 3 hours
Bleeding in excess of 150 mL/minute.
transfusion threshold -rbcs (3 reasons you might not stick to threshold, what the usual threshold and targets are, 2 things to check after each unit is transfused)
Use restrictive red blood cell transfusion thresholds for patients who need red blood cell transfusions and who do not:
* have major haemorrhage or
* have acute coronary syndrome or
* need regular blood transfusions for chronic anaemia.
When using a restrictive red blood cell transfusion threshold, consider a threshold of 70 g/litre and a haemoglobin concentration target of 70–90 g/litre after transfusion.
Consider a red blood cell transfusion threshold of 80 g/litre and a haemoglobin concentration target of 80–100 g/litre after transfusion for patients with acute coronary syndrome
after each single unit transfusion check clinical status and Hb level
after 3 units check iCal level and consider giving Ca IV, as each bag of red cells contains citrate to stop coagulation, and this take a while to metabolise esp in ppl with liver failure
transfusion reactions (coagulopathy and how managed, 2x electrolyte abnorms, hypotherm, acute haem reaction, TACO, TRALI, mild/strong allergy, non-hae febrile reaction, 6x transfuion infections, GvHD, iron overload)
transfusion reactions: Clotting abnormalities can occur due to a dilution effect, as the packed red cells transfused do not contain any platelets or clotting factors. Specific conditions like trauma also in themselves can cause coagulopathy. Also risk of hypocalcemia due to citrate in the pRBCs causing coagulopathy
To reduce the risk of any clotting impairment, fresh frozen plasma and platelets should be administered concurrently, typically done for patients receiving more than 4 units RBCs*. Also consider IV Ca (at least check iCal)
two main electrolyte abnormalities that can occur in blood transfusions:
Hypocalcaemia – Chelation of calcium by the calcium binding agent in the preservative results in a reduced serum calcium level
Hyperkalaemia – Due to the (inevitable) partial haemolysis of the red blood cells and the resultant release of intracellular potassium
As blood products are thawed from frozen and then kept at cool temperatures, they may not be up to body temperature by time of transfusion, especially in a major haemorrhage protocol scenario. Rapid transfusion of these products can lead to a drop in the patient’s core temperature, hence regular monitoring of core body temperature is always required during a blood product transfusion.
transfusion-specific complications can be divided into acute and delayed complications
Acute haemolytic reaction (ABO Incompatibility) is a serious reaction caused by transfusion of the incorrect blood type, the most common cause being ABO blood group incompatibility. Donor red blood cells are destroyed by the recipient’s preformed antibodies, resulting in haemolysis.
Patients will present with urticaria, hypotension, and fever, and may have evidence of haemoglobinuria from the rapid haemolysis. Blood tests will show a reduced Hb, a low serum haptoglobin, and high LDH and bilirubin; a positive Direct Antiglobulin Test (DAT) will confirm the diagnosis.
Urgently inform blood bank that you suspect this has happened, as they may have dispensed further incorrect blood. Stop the transfusion and begin supportive measures, with fluid resuscitation and O2 supplementation
Transfusion Associated Circulatory Overload (TACO) presents with dyspnoea and features of fluid overload. This is often a common problem in those who are already overloaded, such as those with cardiac failure.
Obtain an urgent chest radiograph, and for those whose diagnosis is confirmed, treatment is via oxygen and diuretic therapy
TRALI: a form of Acute Respiratory Distress Syndrome (ARDS), a non-cardiogenic cause of pulmonary oedema. Patients are dyspnoeic and have features of pulmonary oedema on clinical examination.
These patients have a high mortality. Start patients on high flow oxygen and obtain an urgent chest radiograph
Other Complications
Mild Allergic Reaction – The patient will complain of pruritus (itching). Treatment is with an anti-histamine such as chlorphenamine. Often the transfusion can be continued, however the patient should be kept under close observation.
Non-Haemolytic Febrile Reactions – An unpleasant, but usually non-life threatening reaction found in 1-2% of patients. The transfusion should be stopped and the patient given antipyretics (e.g. paracetamol) and anti-histamines (e.g. chlorphenamine).
Anaphylaxis – Presents with hypotension in the presence of anaphylactic symptoms. Stop the transfusion and treat as you would normally for anaphylaxis.
delayed: Infection – There is a theoretical risk of developing any of Hepatitis B, Hepatitis C, HIV, syphilis, malaria, or vCJD with any blood transfusion. Fortunately, these are less of a concern in recent years due to screening of blood donors
Graft vs. Host Disease (GvHD) – GvHD occurs due to an HLA-mismatch between donor and recipient. It is most common in the transfusion of non-irradiated blood products to an immunocompromised recipient. Clinical features include a fever, skin involvement (ranging from macropapular rash to toxic epidermal necrolysis - often how it begins) and diarrhoea and vomiting; may also present acutely esp in allogeneic bone marrow transplants (hence importance of HLA matching), and have abdo pain
Iron overload – Most common in patients that receive repeated transfusions, such as in thalassaemia
blood transfusion special requirements - purpose of irradiation, 3 things to irradiate, 2 not to, 10 pts who need, 6 who don’t
irradiated (like leucodepleted but better) is needed to prevent graft versus host disease
Products requiring irradiation: Red cells, platelets, granulocytes.
Products not requiring irradiation: plasma components – FFP, cryoprecipitate
if hodgkins lymphoma, bone marrow/HSC transplant, treatment with certain haemat chemo agents, congen immunodef, CAR-T cell therapy, alemtuzumab, aplastic anaemia with ATG treatment, any transfusion from 1st/2nd deg relative, intrauterine, neonate needing exchange transfusion
don’t normally need for NHL, leukaemia (unless on those chemo drugs), solid tumours, organ transplants, HIV or other acquired immunodef, aplastic anaemia (unless ATG treatment)
passenger lymphocyte syndrome
an immune mediated haemolysis that can occur following ABO (or misc other antigens) mismatched solid organ transplantation
Occurs when viable lymphocytes from the donor are transferred to recipient and make antibodies that can cause haemolysis
Anaemia induced by PLS is usually abrupt in onset; associated with a positive Direct Antiglobulin Test (DAT)
transfusing the pt may not improve the anaemia - need blood that matches donor antigen too
