Haematology Flashcards
Which anticoagulant is teratogenic
Warfarin
- especially if taken week 6-12 pregnancy
Heparin doesnt cross the placenta
Aspirin in high doses can cause premature closure of ductus arteriosus
Thalassemia
imbalance between alpha and beta globin chain production ie problem with quantity of globin
alpha - less alpha globin (normal= 4 genes); beta - less beta globin (normal = 2 genes)
Alpha characterised by increased Hb Barts (tetramer of gamma Hb)
Beta characterised by elevated A2 (alpha + delta)
Alpha thalassemia
1-4 gene deletions
1 gene deletion: clinically silent
2 gene deletion: normal or mild anemia
Moderate Barts (5-10%)
2 gene deletion + constant spring: mod -severe anemia
B0 thalassemia
No beta globin produced by that allele
If homozygous= no beta chains at all
unable to make HbA (only HbF/HbA2)–> severe anemia, transfusion dependant, haemochromatosis –> death
B+ thalassemia
B+/B+
B+= Reduced amount of normal beta globin
Moderate anemia, may be transfusion dependant
Less severe than B0
Produce up to 50% HbF, >4% HbA2, HbA ~50%
Beta thalassemia major
B0/B0, B0/B+, B+/B+ or compound heterozygote with HbE
progressive haemolytic anemia from ~6 months (when HbA is supposed to predominate), transfusion dependant from early age (<2 years)
clinical/phenotypical diagnosis
A globin tetramers form and appear as red cell inclusions; very unstable, reduce red cell survival –> anemia, increased (but ineffective) erythropoesis with early erythroid precursos death in BM (inappropriately low reticulocyte count) + compensatory massive BM expansion with thalassemic facies + maxilla hyperpasia/frontal bossing/HSM
HbF (alpha + gamma) >90%,HbA2 (alpha + delta) >5% no or very little HbA
Can be diagnosed at birth as no /very little HbA (only HbF)- normally 20% HbA at birth
beta thalassemia intermedia
less severe phenotype
Mod anemia but not transfusion dependant in childhood; may only be transfusion dependant during infection/pregnancy
usually B+/B+ or B0/B+
HbF up to ~60%, HbA up to ~40%, HbA2 >4%
B thal minor
AKA beta thal trait
Carrier
Mutation in only one beta globin gene
- either B+/B or B0/B
- only need one notmal gene to produce enough beta globin
Asymptomatic or mild microcytosis +/- anemia
Slightly elevated HbA2 3-7% HbF 1-3%, HbA >90%
Alpha 0 mutation
no alpha chains produced from that gene
Alpha + mutation
reduced alpha chains produced from that gene
major difference between sickle cell anemia and thalassemia
sickle cell- quality of globin produced
thalassemia - quantity of globin produced
What is Bart haemaglobin
Tetramer of gamma chains
Occurs in alpha thalassemia due to excess gamma chains when alpha chains cant be produced to form normal fetal haemaglobin
After birth this becomes HbH (tetramer of beta globins) when gamma chains stop being produced
What is HbH?
Tetramer of beta globins
Due to no alpha chains in alpha thalassemia
Complications of thalassemia
Anemia - can lead to high output heart failure, FTT
Skeletal abnormalities from BM enlargement
Iron overload from transfusions- toxicity in various organs, hypogonadism, hypothyroidism, insulin resistance growth impairment
Complications of hemolysis: jaundice, pigment gallstones
Hepatosplenomegaly (extramedullary hematopeisis in liver and spleen, hepatic iron deposition, hemolysis)
Hypersplenism –> pancytopenia
Liver fibrosis and cirrhosis
Venous thrombosis
Osteopenia/osteoporosis /bone pain
HbH disease
3 alpha chains affected
usually have symptomatic anemia at birth
May have pigment gallstones
HbH up to 30%, HbA2 up to 4%
Newborn screening for haemaglobinopathies
Normal adult and neonate haemaglobin studies
Adult: HbA 96-98%, HbA2 2-3%, HbF <1%
Neonate: HbF 80%, HbA 20%, HbA2 0%
Haemaglobin studies in beta thal trait
Elevated HbA2 >3.5%, HbF 1-4% (ie both slightly eleveated compared to normal) HbA 92-95%
Haemaglobin studies in beta thal major
Very low or no HbA, only HbF (95-98%), HbA2 (2-5%
this is detectable from birth (should have 20% HbA at birth >36 weeks)
*consider b thalassemia intermedia or major in a bub with <5% HbA (if born >36 weeks)
The absence of HbA (even at birth) is pathomenmonic for beta thal major
Hb Barts in newborns haemaglobin studies
In all newborns with α-thalassaemia the non functional abnormal fraction Hb Bart’s will always be detected. To some extent, the amount of Hb Bart’s correlates with the number of defective α-globin genes. A simple mild condition with a single gene defect (-α/αα) will present with very little Hb Bart’s (1-4%), while in samples with two defective α-genes, either in cis (–/αα) or in trans (-α/-α), the Hb Bart’s will rise to 5-15%, reaching 25% and higher in HbH disease with 3 defective α-genes (–/-α) (13-15).
Can a B thalassemia carrier be detected at birth?
Only intermedia or major can be detected by measuring HbA levels
HbA2 is not significantly expressed until 1 year of age to be used as a diagnostic parameter
Carriers would have HbA««20% but there is wide variation of “normal” so not really able to diagnose until later
haemaglobin studies in beta thal intermedia
HbA 10-30%
HbF 70-90%
HbA2 2-5%
co inheritance of alpha trait with homozygous beta thal major leads to…
reduction in alpha globin synthesis reduces burden of alpha globin inclusions so improves the phenotype
can change tranfusion dependant thal major to non transfusio dependant thal intermedia
what infections are increased in thalassemia major
Yersinia enterocolitica - iron loving, iron chelation makes it even more available
Listeria
Salmonella
how do you reduce the risk of iron overload in transfusion dependant thalassemia
Chelation with desferrioamine (subcut/IV)- ototoxicity, retinal changes, cataracts, GI side effects, yersinia infections)
Desferasirx - oral tds (a/e- GI, renal)
Deferiprone - oral tds (A/e- agranulocytosis, deranged LFTs, arthralgia, arthropathy
Differentiating iron deficiency from thalassemia minor
iron def - low retics, low RBC count, low ferritin
thalassemia - normal or slightly increased retics, high RBC
Iron studies in thalassemia- elevated ferritin and transferrin saturation (even without transfusion )
Low ferritin is only seen in thalassemia if there is a concomitant iron deficiency
Film in thalassemia: nucleated RBC, target cells, anisopoikolocytosis
how does iron def interfere with the diagnosis of beta thal minor
reduces the amount of HbA2 which is the main diagnostic feature in beta thal minor
Haemaglobin constant spring
The most common non-deletional alpha globin variant is hemoglobin Constant Spring.
In contrast to beta thalassemias, in which beta+ variants tend to be less severe, some alpha+ alleles such as Hb Constant Spring can actually aggravate severity. This is because the common alpha+ alleles encode alpha chains that, when combined with beta chains, create highly unstable hemoglobins that precipitate, adding to the burden of inclusion bodies in the developing and circulating RBCs.
1 alpha globin deletion leads to ..
silent carrier
maybe microcytosis
can only be detected on genetic analysis
2 gene deletion /mutation in apha globin gene leads to..
alpha thalassemia trait
microcytosis +/- silent carrier
Slightly elevated Hb barts in newborn period; otherwise electrophoresis is normal
3 gene alpha globin mutation leads to
HbH disease
can be deletional or non deletional (more severe- constant spring)
Moderate haemolytic/microcytic anemia
Electrophoresis: Elevated HbH (up to 30%), elevated HbA2 ~4%
HbH has virtually no oxygen transport capacity and is insoluable, so precipitates out of RBC leading to haemolytic anemia
2 alpha deletions + constant spring mutation (compound heterozygote) leads to a more severe anemia with more frequent hemolytic events and earlier mean age at first transfusion
4 gene deletion of alpha globin leads to
severe hemolytic anemia in utero–> hydrops fetalis
Only Hb is Hb barts (tetramer of gamma chains)
only survive with exchange transfusions
when do you see Hb Barts
elevated in all newborns with alpha thalassemia mutations (carriers/trait/HbH)
How do you diagnose alpha thalassemia
alpha trait/minor- only by DNA testing
Electropheresis can show Hb Barts or HbH in a neonate with alpha thal
Hb Barts of 20-40% within 2 days of birth is a hallmark of HbH disease in newborn
Low levels of Hb Barts (3-8%) or no Hb Barts is diagnostic of alpha thal minor
If above findings are present, need to do gene analysis
Fanconi anemia
AR
Bone marrow failure
Increased chromosomal breakage, poor DNA repair
Pancytopenia
Skin- hyperpigmentation, cafe au lait
Short stature
Thumb/radia abnormalities
Genital problems
(ddx diamond blackfan anemia- usually red cell aplasia)
Dyskeratosis congenita
bone marrow failure syndrome
short telomeres (defect in telomere maintenance)
diagnosed by telemere length analysis
Triad: lacy skin pigmentation, dystrophic nails, oral leukoplakia
Schwachman -Diamond syndrome
Bone marrow failure syndrome
Triad: exocrine pancreatic insufficinecy, neutropenia, metaphyseal dyspasia
Risk increased with monosomy 7
heinz bodies are seen in
G6PD deficinecy - oxidative stress leading to denatured haemaglobin
Alpha thalassemia (excess of beta chains precipitating as HbH)
Hyposplenism eg sickle cell anemia
haemolytic uremic syndrome presentation
triad of microangiopathic haemolytic anemia, thrombocytopaenia and acute kidney injury with concurrent gastroenteritis is suggestive of shiga-toxin producing E. Coli
MoA hydroxyurea
Increased HbF production
shift in gene expression at the beta globin gene locus, leading to a relative increase in gamma globin gene expression and hence increases production of HbF (2 alpha and 2 gamma chains) with relative reduction in HbS. Reduction in HbS leads to increased RBC lifespan, reduced haemolysis and reduced microvascular adhesion, improving microcirculation.
Evans syndrome
Autoimmune haemolytic anemia + thrombocytopenia
HbSC
clinically significant sickle cell variant syndrome. It is less severe than sickle cell disease, and more severe than sickle cell trait. Patients will HbSC are at the same risk of life threatening crises as (painful episides, strokes), lower risk bacterial infection, patients with HbSS but these occur less frequently with milder clinical severity.
sickle cell anemia
homozygous Hb SS (both beta globin alleles have the sickle cell mutation.)
Hb S 85-95% of total Hb
sickle cell disease
either sickle cell anemia (homozygote) or compound heterozygote with beta thal or Hb C/D/E
>50% HbS
Hb studies in HbSS
HbA = 0
HbF 5-15%
HbS 85-95%
HbA2 <3.5%
Neonate: FS
Hb studies in sickle B0 thal
HbA= 0
HbF 2-15%
HbS80-90%
HbA2 >3.5 (rememeber beta thal has elevated HbA2!)
Neonate: FS
Hb studies in sickle B+ thal
HbA 3-30%
HbF 2-10%
HbS 60-90%
HbA2 >3.5 %
Neonates: FS or FSA
Hb studies in HbSC
HbA = 0
Hb F 1-5%
HbS 45-50%
HbC 45-50%
HbA2 <3.5
what is the most common cause death in sickle cell disease
infection
Almost all patients become functionally asplenic by age 5 years and are at risk for severe infection and sepsis (particularly by encapsulated organisms).
Low threshold for antibiotics if any hint infection
Penicillin prophylaxis at diagnosis/by 2 months of age until at least 5 years
* All sickle cell patients should be treated as if they are functionally asplenic and at risk from invasive disease with encapsulated organisms * If pain is also present treat concurrently as VOC * If cough or dyspnoea also present look and treat for acute chest syndrome (see below) * Commence antibiotics without delay if febrile or toxic: o Cefotaxime IV 50mg/kg (max 2g/dose) every 6 hours OR Ceftriaxone IV 100mg/kg (max 4g/day) once daily.
acute chest syndrome
- Acute Chest Syndrome (ACS) is defined as a new pulmonary infiltrate on CXR AND any one of :
o fever
o tachypnoea
o cough
o hypoxia(O2Sats<96%)
o increased work of breathing
o chest pain
due to infarction of lung tissue.
DDx pneumonia so treat with IV abx as well
Rx: O2
IV abx
analgesia
Trial inhaled bronchodilators +/- steroids
Small volume blood transfuson (aim Hb <100 post transfusion (above this risks hyperviscosity)
If severe: exchange transfusion
Acute splenic sequestration
Defined as a Hb drop of at least 20g/L below baseline in a patient with an acutely enlarged spleen
Abdo pain, acutely enlarged spleen, anemia, thrombocytopenia, low retics
Rx: PRBC transfusion (but not above usual baseline, risk hyperviscosity). IVF while waiting for blood if haemodynamically unstable
Treat with IV abx as often triggered by bacterial or viral infections
Consider prophylactic splenectomy if repeated episodes
Only give enough blood to prevent haemodynamic instabiliy eg 5ml/kg
risk autotransfusion - where blood sequestered in spleen is released and dramatically increases the Hb concentration, putting patient at risk for hyperviscosity syndrome
Sickle cell anemia treatment
Hydroxyurea (increases HbF production)
Prophylactic penicillin
PRBC for anemia, complicated VOC episide,s aplstic crisis (eg w infection), ACS, splenic sequestration
Extra immunisations as functionally asplenic
HSCT curative
What surveillance is required in sickle cell disease
- complications of many blood transfusions: monitor ferritin for iron overload, trasnmitted infections, anual audiogram/LFTs/pituitary function if chelation used
- Transcranial doppler USS for stroke prevention, annually ages 2-16 years
- Asthma screening- increased risk
- Retinopathy- annual screening from age 10
- Renal - annual urinalysis from age 10
- Echo- screening for pulmunary artery HTN
Haemophilia A and B overview
Factor 8 and factor 9 deficiency
A much more common than haemophilia B
X linked
1/3 of female carriers will have reduced F8/9 levels due to skewed X inactivaion; if levels <40% should be managed as per male counterparts with hemophilia. if turners- present as males
Clinically indistinguishable
Bleed for longer, due to longer time to develop clot, and this clot is soft and friable, increased risk of rebleeding
Severe: <1% activity –> spont bleeding
moderate : 1-5% activity, mild trauma can induce bleeding
mild: >5% activity, need significant trauma to induce bleeding
common precipitants for vaso occlusive crisis
physical stress
infection
cold
dehydration
hypoxia
acidosis
swimming for prolonged periods (stress + cold)
hydroxyurea adverse effects
gastritis, mucositis skin ulceration
pneumonitis
myelosupression
secondary leukemia
**specific for S phase in cell cycle
Coagulation studies in haemophilia
Prolonged APTT
Normal PT/INR
Normalisation of APTT with mixing studies (unless inhbitor is present)
Treatment hemophilia
Factor replacement (usually recombinant)
On demand (if mild) vs prophylactic (if mod-severe)
Factor first principle on presentation to ED
Mild hemophilia A - DDAVP
TXA as adjunct for mucosal bleeding
Hemophilia prophylaxis
Extended half life F8or F9
Emicizumab (Hemlibra) for hemophilia A
Hemlibra is a subcut injection 2-4 weekly
- monoclonal antibody (not immunogenic), Factor 8 mimic (ie mimics function of F8, brings together 9a and 10, substituting role of factor 8a
- still need F8 or rF7a if inhibitor present, for acute bleeding episodes, but Hemlibra turns severe HA into mild phenotype
Inhibitors in hemophilia
Factor 8 and 9 are immunogenic who have absent or mutated F8 and 9
Development of allo-antibodies increases with increased severity of hemophilia phenotype (20-30% in severe HA, 10% in mild HA, 3-5% in HB)
**severity is the biggest risk factor for development of inhibitors **
High level inhibitors render factor therapy ineffective
therefore bypassing agents (recombinant activated factor 7) are required to manage bleeding
Low level inhibitors can be overcome by using a higher dose of factor
Acute management of bleeding in haemophilia
Aim replacement of factor
Mild - modL aim 35-50%
severe- aim 100 %
calculations
dose rF8= % desired rise x bodyweight in kg x 0.5
dose rF9= % desired rise x bodyweight in kg x 1.4
Treatment choice in haemophilia A
Prophylactic recombinant factor VIII infusions (usually 2-3 times per week) or Emicuzumab (Hemlibra) 204 weekly
Recombinant factor VIII pre op or post injury/bleeding
DDAVP in mild disease - this raises the patient’s own factor VIII levels
Tranexamic acid can be given with DDAVP for mucosal bleeding
Causes prolonged PT
Isolated PT prolongation:
Deficiency in F7 ,
Liver disease
Vit K deficiency (mild)
Vit K antagonist eg warfarin
DIC
Prolonged PT and APTT
Deficiency in F10, F5, F2, F1
Liver disease
DIC
Severe vit K deficiency
Warfarin
Causes prolonged APTT
Deficiency in F8, 9, 11, 12
vW disease
heparin
lupus anticoagulant
To which protein does heparin bind?
anti thrombin 3
which regulates thrombin (F2) and FXa
—> increases its anticoagulant effect, enhances the rates at which antithrombin III inactivates activated clotting factors,
To which protein does heparin bind?
anti thrombin 3
which regulates thrombin (F2) and FXa
—> increases its anticoagulant effect
Thrombin actions
Activates F5 and F8
Activates plateets and promotes platelet aggregation
Activates FI to Fia (fibrinogen to fibrin)
Activates F13 to F13 a (stabilising factor)
what factors prevent platelets from adhering to normal tissue
nitric oxide
prostacyclin
Also makes activated platelets produce less Thromboxane A2
Role thromboxane A2
- Platelet activator
Causes platelets to produce GPIIB/IIIA on their cell membranes, which allows platelets to bind to fibrinogen - Vasoconstricter
What is the role of GP1a
expressed on cell membrane of platelets
Allows them to bind vWF (bound to collagen) - thus allows platelets to bind to collagen
Thrombin time
Thrombin time (TT) measures the final step of coagulation, the conversion of fibrinogen to fibrin
The thrombin time is prolonged if fibrinogen levels are low or if an anticoagulant that inhibits thrombin (eg heparin) is present in the sample.
what do increased fibrin degredation products imply
DIC
reptilase time is normal with..
heparin
heparin gives prolonged APTT, TT but normal repilase time
HbE
- reduced expression of beta globin (therefore clinically functions as a beta thalassemia phenotype)
HbE-beta 0 thal is a moderate-severe thalasemia which can be transfusion dependant
low fibrinogen is seen in .
liver disease
DIC
Echis time is normal in which conditions
Vitamin K deficiency
Warfarin
Prolonged in liver disease
what is the average lifespan of platelets
10 days
Glanzmann thrombasthenia
hereditary platelet disorder
AR
platelets cant aggregate, despite intact signalling
Due to loss/dysfunction of GPIIb/IIIa
Leads to severe bleeding starting in neonatal period
Normal platelet number and size
Carriers are asymptomatic
Similar presentation to type 3 vWD
Think of this with history of neonate wth ooze around umbi/petechiae/purpurae/gingival bleeding
Bernard Soulier syndrome
AR
Thrombocytopenia with giant platelets
Moderate-severe beeding
Defects in GP1b (cant bind to VWF) –> cant form primary platelet plug
Thrombocytopenia due to reduced survival
Platelet aggregation tests show absent ristocetin-induced platelet aggregation,
but normal aggregation to all other agonists.
MYH9 platelet disorders
AD
Large platelets
Thrombocytopenia
Platelet dysfunction
Bleeding phenotype is mild
mutation in MYH9 gene
Associated with cataracts, SN hearing loss, glomerulonephritis
think Alport phenotype but in females, and large platelets
X linked thrombocytopenia
XLR (like WAS)
Mod to severe thrombocytopenia with small platelets
Mutations in WAS gene
May have very mild immune deficinecy
Splenectomy can improve platelet count
Immune thrombocytopenia (ITP)
Diagnosis of exclusion
Otherwise normal FBE and normal exam (no organomegaly, no bone pain, no constitutional symptoms, no lymphadenopathy)
Usually follows viral illness
if >12 mo= chronic
Rx:
Dont really need to treat unless bleeding as severe haemorrhage is rate
Treat if GI bleeding/hematuria etc
prednisolone
IVIG if need to raise platelets fast
Chronic ITP: rituximab, splenectomy if failure of medical management >12 mo or life threatening bleeding
what effect do carbomazepine and phenytoin have on neonatal bleeding risk
increased risk of vitamin K deficient bleeding
what blood type combination reduces the risk of haemolytic disease of the newborn
Rhesus negative mum with rhesus positive baby AND ABO incompatibility (mum O and baby A or B)
Grey platelet syndrome
AR
Absense of alpha granules in platelets
thrombocytopenia + bruising tendancy
Chedak Higashi syndrome
primary immunodeficiency with defective phagolysosome formation
Albinism
Bleeding tendancy
Peripheral neuropathy
Differentiate from Hermansky-Pudlak syndrome (also have oculocutanous albinism) by giant neutrophil intracytoplasmic granules on blood smear
tried in HUS
microangiopathic anemia
thrombocytopenia
acute kidney injury
Encapsulated bacteria
strep pneumoniae
h. influenze
klebsiella kingae
pseudomonas auruginosa
E.coli
salmonella
what cancer is CAR T cell therapy used for
ALL
hereditory spherocytosis
haemolytic anemia (DAT neg), usually low MCV
increased retics
may have jaundice, splenomegaly, aplastic anemia with parvo b10
Ix: EMA binding low , increased osmotic fragility testing
warm autoimmune haemolytic anemia
most common form of AIHA in kids
IgG brings to red cells at 37C leading to extravascular hemolysis (spleen) –> anemia, jaundice +/- splenomegaly
DAT pos IgG at 37C
Caused by:
Primary (idiopathic)
Autoimmune/autoinflammatory disorders (SLE, Sjogren, AIA, T1DM, thyroiditis)
Evans syndrome
Primary immunodeficinecy
HIV
Malignancy
Post transpant
Post infection (less common, usually cold)
Rx; steroids
autoimmune haemolytic anemia
a collection of disorders characterized by the presence of autoantibodies that bind to the patient’s own erythrocytes, leading to premature red cell destruction (hemolysis) and, when the rate of hemolysis exceeds the ability of the bone marrow to replace the destroyed red cells, to anemia
Cold agglutinin disease
Cold heamolytic anemia
must less common than warm AIHA
IgM autoantibodies bind to antigens on RBC at colder temperatures and fix complement –> complement mediated intravascular hemolysis or immune mediated extravascular clearance by macrophages
Intravascular haemolysis —> hemaglobinuria
Ix: DAT pos for C3, neg for IgG
Clumped RBC on film
Usually secondary to infection - EBV or mycoplasmia pneumoniae
Rx: avoid cold
paroxysmal cold hemoglobinuria
AIHA
usually after viral illness
IgG autoantibodies target P antigen on RBC
intravascular hemolysis w hemaglobinuria, and anemia
Ix: DAT pos for IgG and C3 at 4C, pos for C3 only at 37C
Heparin MoA
a naturally occurring anticoagulant released from mast cells.
It binds reversibly to antithrombin III and greatly accelerates the rate at which ATIII inactivates coagulation enzymes thrombin (factor IIa) and factor Xa.
By inactivating thrombin, heparin not only prevents fibrin formation but also inhibits thrombin-induced activation of platelets and of factors V and VIII.
Antithrombin 3
Antithrombin III inhibits clotting factors IIa (thrombin), Xa, and to a lesser extent IXa and XIIa. UFH and LMWH bind to antithrombin III via a pentasaccharide group, inducing a conformational change which enhances antithrombin-mediated inhibition of these clotting factors
Which conditions lead to falsely high or falsely low HbA1c
Anything that shortens the lifespan of RBC will
cause incorrectly low HbA1c- eg thalassemia, sickle cell anemia,
hereditory spherocytosis
Vit B12 deficiency and iron deficiency will make them falsely elevated
heparin induced thrombocytopenia associated with
platelet factor 4 complex
what sedation is contraindicated in B12 deficiency and why
nitric oxide
risk of subacute combined degeneration of spinal cord
NO inactivates B12 and inhibits methionine synthetase -> disrupts methylation and DNA synthesis
blood film findings in autoimmune hemolytic anemia
Macrocytic anemia w reticulocytosis
Rouleaux + agglutination
what cleaves fibrin
plasmin breaks down fibrin mesh
what activates factor 7
tissue factor
reprilase time is prolonged with
low fibrinogen
reptilase time can be used to differentiate cause of prolonged thrombin time
if reptilase time is normal: heparin present
if reptilase time prolonged: low fibrinogen causing prolonged TT
von willebrand disease
· Type 1:
· AD
· Partial quantitative deficiency of von Willebrandfactor
· Low VWF levels and activity
· F8 mildly low
· Ristocetin normal
· Type 2: · AD · Qualitative defects invonWillebrand factor · 2A is the most common variant · Type 2A: the activity is proportionally much less than the VWF level, the factor 8 is not markedly low, the ristocetin is decreased, and you see less multimers specifically on electrophoresis. · Type 2B: same, the activity is proportionally much less than the VWF level, the factor 8 is not markedly low, the ristocetin is increased, you get low Plt and may also see less large multimers but less than in Type 2A. - basically because it binds too well to plts and gets cleared more. If you have low Plts, really think of type 2b. · Type 2M: get same features as type 2a, but all multimers uniformly decreased, not just large ones, plts fine. Due to abnormal binding of the VW factor to platelet glycoprotein. Also low risto as for type 2a. · Type 2N: the VWF doesn't bind well to factor 8 and cant protect it, here its activity at Plt aggregation etc are fine so activity, and antigen are normal, risto is normal, but have low Factor 8 and abnormal APTT. · Type 3: · AR · Complete quantitative defect- VWF levels are not detectable severe bleeding · Almost absent F8 (rapid breakdown) · Low ristocetin
which factors are found in cryoprecipitate
Factor 8
Factor 13
Fibrinogen
VWF
HUS
Present with fever, diarrhoea (bloody), bruising, hematuria.
Microangiopathic hemolytic anemia and thrombocytopenia.
Schistocytes on blood smear
The Coombs test is negative, consistent with mechanical hemolysis.
Elevated retics
Chem20: elevated creatinine consistent with acute kidney injury.
It also shows signs of acute hemolysis with elevated indirect bilirubin and elevated lactate dehydrogenase.
As the disease progresses, hyponatremia and hyperkalemia may develop as the patient enters into renal failure.
Urinalysis reveals hematuria and proteinuria.
Rx: Supportive
Admission +/- PICU
Fluids, PRBC, dialysis
Avoid antibiotics as this can worsen toxin production
HbSC
a clinically significant sickle cell variant syndrome. It is less severe than sickle cell disease, and more severe than sickle cell trait. Patients will HbSC are at the same risk of life threatening crises and patients with HbSS but these occur less frequently with milder clinical severity.
Hb C
Homozygosity for Hb C (Hb CC disease) can present in infancy, older childhood, or adulthood, depending on other factors that affect clinical severity. Hb CC (homozygous) disease causes mild hemolytic anemia and often splenomegaly without vaso-occlusive manifestations. More severe disease can occur when Hb C is combined with a severe beta globin variant. Heterozygosity for Hb C is an asymptomatic carrier state
Compound heterozygosity for Hb C and Hb S causes Hb SC disease, a form of SCD. The clinical severity is usually less than that in individuals with homozygous Hb SS or Hb S-beta0 thalassemia
Hb E
Hb E causes a beta thalassemic phenotype and is mildly unstable to oxidative damage. Homozygotes have minimal anemia with hypochromia, target cells, and prominent microcytosis.
Individuals who are homozygous for Hb E have mild microcytic anemia (microcytosis > anemia). Target cells can be seen on blood film.
Hb E in combination with beta thalassemia can range from mild to moderate to severe depending on the other beta globin variant. Over half of individuals with Hb E plus beta0 thalassemia are transfusion dependent. Heterozygosity for Hb E is an asymptomatic carrier state.
clinical triad for neonatal renal vein thrombosis
haematuria, palpable flank mass, and thrombocytopenia
Pathenemonic finding in beta thalassemia
increased HbA2 >3.5
NOTE: may not have significantly elevated HbA2 if concurrent iron anemia
which cells are seen in blood film in thalassemia
target cells
teardrop cells (also b12 deficiency)
what is most commonly seen in blood film in warm autoimmune hemolytic anemia
spherocytes
red cell clumping in cold AIHA
what are pencil cells suggestive of
iron deficiency
what factor decreases the risk of maternal sensitsation (in terms of hemoytic disease of newborn)
ABO incompatibility
The risk of sensitization to the Rh D antigen is decreased if the fetus is ABO incompatible. This is because any fetal cells that leak into the maternal circulation are rapidly destroyed by potent maternal anti-A and/or anti-B, reducing the likelihood of maternal exposure to the D antigen.
most common hypercoagulable condition
activated protein c resistance due to factor 5 leiden mutation
Half lives of clotting factors
F7: 3-6 hours
F8: 12 hours
F9: 24 hours
F10: 24-48 hours
F2: 60 hours
Protein C - 8 hours
Protein S - 30 hours
most common dietary factor associated with iron deficinecy anemia
introdcution of cows milk prior to 8 months
high volumes of cows milk
how quickly will a reticulocyte response be seen in iron deficiency anemia when iron is started
3 days
bite cells seen in …
G6Pd deficiency
VWF:RCo (ristocetin cofactor)
VWF:RCo is an assay that measures the ability of VWF to bind to platelet membrane receptor GPIb. Ristocetin is an antibiotic that is no longer clinically used because it causes platelet aggregation. However, this means that it is a useful drug in the laboratory. It is added to patient plasma along with washed or formalin-fixed platelets, and the amount of functional VWF in the plasma that causes platelet agglutination is quantified using platelet aggregometry or a manual (tilt tube) method. In contrast, Plasma von Willebrand factor antigen (VWF:Ag) measures the quantity of VWF protein in the plasma.
which baceria causes osteomyelitis in sickle cell anemia
salmonella
Pulse oximetry is widely utilised in clinical practice to measure the oxygen saturation of haemoglobin. In which of the following situations is the measured saturation likely to be falsely elevated?
methaemglobinemia
what is Hb Barts made u of
4 x gamma chains
