core haematology Flashcards
what is haemopoiesis?
the physiological development process that gives rise to the cellular components of blood
what is the name of the cell which can divide and differentiate to form different cell lineages that will populate the blood?
multipotent haemopoietic stem cell
what is the difference between symmetric and asymmetric self-renewal of a haemopoietic stem cell?
symmetric: stem cell divides to create 2 more stem cells
asymmetric: stem cell divides to create 1 stem cell and 1 (more specialised) progenitor cell
(nb can also have ‘lack of self renewal’ when one stem cell divides to create 2 progenitor cells)
which blood cells are in the lymphoid lineage and which are in the myeloid lineage?
everything is from the myeloid lineage, EXCEPT:
- B-lymphocytes
- T-lymphocytes
what is the difference between monocytes and neutrophils?
monocytes
- become macrophages when get into tissue (circulate blood as monocytes)
- long lived
- antigen-presenting
neutrophils
- short lived
- not antigen-presenting
what is the lifespan of a RBC?
3 months/ 120 days
in the EARLY developing embryo, where does haemopoiesis occur?
(originally slightly in yolk sac)
but mainly in EMBRYONIC PLATE (between amniotic sac + yolk sac)
where does haemopoiesis occur in the developing foetus?
Aorto-gonado-mesonephros (AGM)
at day 40, the haemopoietic stem cells migrate, via the aorta, to the foetal liver (which become the subsequent site of haemopoiesis
what is the name given when there are too many RBCs?
polycythaemia
what is relative polycythaemia?
when plasma volume is REDUCED (but no. of RBCs doesn’t change)
- therefore there is a higher concentration of RBCs in the blood
what are the three main groups of leukocytes?
- lymphocytes
- monocytes
- granulocytes
what are the three types of granulocytes?
- neutrophils
- eosinophils
- basophils
what is the name given when there are more neutrophils than normal in the blood?
what might cause this? 3
neutrophilia
- bacterial infection
- inflammation
- use of steroids (flush neutrophils out of tissues into blood??)
what is the name given when there are fewer neutrophils than normal in the blood?
what might cause this?
neutropenia
side effects of certain drugs, eg:
- co-trimoxazole (an Abx)
- chemo drugs
what is it called when there are more eosinophils in the blood than normal?
what might cause this? 2
eosinophilia
- parastic infection (eg schistomiasis)
- allergies
what is it called when there are more basophils in the blood than normal?
what normally causes this?
basophilia
myeloma proliferative neoplasms
- especially: chronic myeloid leukaemia
what are the name for the macrophages in the:
- liver?
- skin?
- brain?
liver: kupffer cells
skin: langerhans cells
brain: microglia
what is it called when there are more monocytes in the blood than normal?
when might this occur?
monocytosis
tuberculosis
what is it called when there are more lymphocytes in the blood than normal?
when might this occur?
lymphocytosis
- eg in chronic lymphocytic leukaemia (CLL)
also in glandular fever (infectious mononucleosis) you get lots of ATYPICAL lymphocytes (which look like monocytes, hence the name!)
what is it called when there are fewer lymphocytes in the blood than normal?
when might this occur?
lymphopenia
- post bone marrow transplant
which lymphocyte produces cell-mediated-immunity and which produces humoral immunity?
cell mediated = t cells
humoral = b cells (via soluble antibodies they produce)
what is adaptive immunity and what is innate immunity?
adaptive = t + b lymphocytes
innate = all other white blood cells (ie myeloid lineage)
what is an increased number of plasma b cells called?
what might cause this?
plasmacytosis
benign
- eg response to infection
myeloma
what is the name of the cell which platelets are derived from?
megakaryocytes
what are the 4 main subspecialties of haematology?
- coagulation
- malignant
- non-malignant
- transfusion
what are the constituents tested for in a Full Blood Count (FBC) blood test?
Hb concentration
Red cell parameters:
- MCV (mean cell volume)
- MCH (mean cell Hb)
white cell count (WCC)
platelet count
what are the RBCs called when they have:
- too little Hb?
- too much Hb?
too little: hypochromate (pale)
too much: hyperchromate (dark)
how do coagulation screens test coagulation function?
what are the main three specific tests used? and what are they used for?
by measuring the time taken for a clot to form when plasma (from patient) is mixed with specified reagents
prothrombin time
- used for warfarin monitoring
activated partial thromboplastin time
- used for unfractioned heparin monitoring
thrombin time
- used for diagnosing specific clotting deficiencies
how are diagnostic bone marrow tests carried out?
under local anaesthetic, liquid marrow is aspirated from POSTERIOR ILLIAC CREST of pelvis and a trephine core biopsy is then taken with a hollow needle
when taking blood what things should you make sure to do? 5
- appropriate sample from patient (eg fasting or not etc)
- blood should be filled to line on tube
- mix blood well (a few inversions is fine)
- labble bottle correctly
- keep bottle with request form
what is the definition of a reference range?
the set of values for a given test that incorporates 95% of the normal population
what is the definition of sensitivity?
the proportion of abnormal results correctly classified by the test
what is the formula for calculating sensitivity?
no. true positives / (no. true positives + no. false negatives)
what is the definition of specificity?
the proportion of normal results correctly classified by the test
what is the formula for calculating specificity?
no. true negatives / (no. true negatives + no. false positives)
what might cause mild lymphocytosis? (but be completely harmless)
post-splenectomy mild lmphocytosis
what might cause lymphopenia? (but not be pathological)
3 months post-bone marrow transplant lymphopenia
what conditions cause microcytic anaemia? 5
- iron deficiency
- thalassaemia
- lead poisoning
- anaemia of chronic disease (some)
- sideroblastic anaemia (some)
what conditions cause normocytic anaemia? 6
- after acute blood loss
- renal disease
- bone marrow failure (eg post chemo, infiltration by carcinoma etc)
- mixed deficiencies
- many haemolytic anaemias
- anaemia of chronic disease (some)
what conditions cause macrocytic anaemia? 6
megaloblastic:
- vit B12 deficiency
- folate deficiency
non-megaloblastic
- alcohol
- liver disease
- myelodysplasia
- aplastic anaemia
what is the main symptom of a sickle cell crisis?
excruciating bone pain
what are megaloblastic cells (present in some forms of macrocytic anaemia)?
a type of immature progenitor RBC which didn’t divide like it should and so just kept getting bigger
(called megaloblastic erythropoiesis)
- B12 + folate deficiency
what are three main types of macrocytic anaemia?
what causes them?
megaloblastic anaemia (ie with megaloblastic erythropoiesis)
- vit B12/folic acid deficiency
- myelodysplastic syndrome
macrocytic anaemia with normoblastic erythropoiesis
- eg liver disease, alcohol, hypothyroidism, myelodysplastic syndrome
‘stress’ haemopoiesis
- eg haemolytic anaemia, recovery from blood loss (macrocytosis reflects high reticulocyte, immature RBC, count)
what are myelodysplastic syndromes (MDS)?
what are the two clinical manifestations of these conditions?
a group of cancers in which immature blood cells in the bone marrow do not mature and become healthy blood cells. Early on there are typically no symptoms. Later symptoms may include feeling tired, shortness of breath, easy bleeding, or frequent infections.
- chronic anaemia with survival for several years
- aggressive disease terminating in ACUTE MYELOID LEUKAEMIA
what is an iatrogenic cause of myelodysplastic syndrome?
- complication of treatment with chemotherapy or radiotherapy
who is most likely to be affected by myelodysplastic syndromes?
typially mid-life to older people
occasionally in younger people
why do myelodysplastic syndromes cause anaemia?
because: a mutated stem cell produces a clone of abnormal cells that replaces normal haemopoiesis
abnormal cells:
- show abnormal maturation morphologically
- often die before leaving the bone marrow
- –> peripheral blood cytopenias
so basically the right amount of cells are still made in the bone marrow but, because they’re mutated, they often die before leaving the bone marrow so there aren’t enough cells in the blood
what are the THREE typical abnormalities seen in BLOOD TESTS of patients with myelodysplastic syndrome (MDS)?
what symptoms do each of these abnormalities produce?
anaemia
- fatigue
- dyspnoea (SOB)
neutropenia
- lots of infections
thrombocytopenia
- bruising
- bleeding
what are 3 types of myelodysplastic syndrome (MDS)?
- refractory anaemia
- refractory anaemia with excess blasts
- MDS 5Q- syndrome
what are the ACTIVE treatments for myelodysplastic syndrome? 4
who is suitable for each one?
lenalidomide
(for 5Q syndrome)
azacytidine
(for patients who aren’t well enough to have a bone marrow transplant)
chemotherapy
bone marrow transplant
what are the SUPPORTIVE treatments for myelodysplastic syndromes? 3
- RBC transfusions
- erythropoietin
- platelet transfusions
what treatment would you give to someone who had too much iron in their body? (side effect of RBC transfusions)
give iron chelation to treat iron overload
what is the process which isolates RBCs from donors blood called?
leucodepletion
how long can RBCs be stored?
how long does it usually take to transfuse 1 unit of RBCs?
up to 35 days
1.3-3 hours
what is the definition of a transfusion threshold (trigger)?
the lowest concentration of Hb that is not associated with symptoms of anaemia
(once you go below that threshold, you should transfuse the patient)
(this threshold varys hugely between patients)
what are the body’s mechanisms of adapting to anaemia? 6
what occurs after these methods have been exhausted (or if the body hasn’t had enough time to respond to the anaemia)?
- increase cardiac output
- increase cardiac artery blood flow
- increase oxygen extraction
- increase of RBC 2,3 DPG (diphosphoglycerate)
- increase production of erythropoitin (from kidneys)
- increase erythropoiesis
–> tissue hypoxia –> symptoms of anaemia
what FOUR things could cause a patient’s transfusion threshold to be lower?
basically if their body has a reduced capacity to react to anaemia due to less effective:
- cardiac output
- arterial blood flow
- O2 saturation
- Hb
eg in:
- cardiovascular disease
- respiratory disease
- haemoglobinopathies
- increased age
what are alternative treatments for anaemia? (ie not RBC transfusions) 5
correction of treatable causes of anaemia:
- iron tablets (for iron deficiency)
- B12 injections (for B12/folate deficiencies)
- erythropoietin treatment (for patients with renal disease)
correction of coagulopathy:
- discontinuation of antplatelet agents
- administration of anti-fibrinolytic agents
how much blood does a person have to loose (in an acute setting) in order for a transfusion to be necessary?
about 1.5 litres
why are patients with inherited anaemias (eg thalassaemia) given regular blood transfusions?
what is a possible adverse event of these?
to suppress endogenous erythropoiesis (which produces the abnormal RBCs)
iron overload
what is the ‘shelf life’ of platelet donations?
what is the usual transfusion for one unit of platelets?
5 days from collection
30 mins/unit
why transfuse platelets? 3
treatment of bleeding due to:
- severe thrombocytopenia (low platelets)
- platelet dysfunction
prevention of bleeding
what are the two main contraindications of platelet transfusion?
- heparin induced thrombocytopenia + thrombosis
- thrombotic thrombocytopenic purpura
how is fresh frozen plasma (FFP) stored?
frozen for up to 2 years
- thawed immediately before use
when should fresh frozen plasma be transfused? 3
when shouldn’t it be transfused? 2
- coagulopathy (problems w clotting factors) with bleeding/surgery
- massive haemorrhage
- thrombotic thrombocytopenic purpura
do not transfuse:
- for warfarin reversal
- for replacement of single factor deficiency
what is the treatment for patients who are bleeding due to too much warfarin?
prothrombin complex concentrate (PCC)
basically a lot of plasma-derived Vit K dependent factors - factors 2, 7, 9 + 10
what is a ‘group and screen’ blood test for?
- determination of patient’s ABO + Rh group
- patient’s plasma ‘screened’ for antibodies against other clinically significant blood group antigens
so that blood can be transfused safely (esp in an emergency) wwith a lower probability of adverse events
what is ‘crossmatching’?
donor red cells of the correct ABO and Rh group are selected from the blood bank
(avoid any other groups the patient has antibodies against - detected in screen)
‘crossmatching’ = patient’s plasma is mixed with aliquots of donor red cells to see if a reaction (agglutination or haemolysis) occurs
if no reaction: RBC units compatible!
if reaction: RBC units INcompatible, risk of acute haemolysis
what is the difference between an acute transfusion reaction and a delayed one?
acute reactions present: <24hr after transfusion
delayed reactions present: >24hr after transfusion
what are the possible acute transfusion reactions (to a blood transfusion)? 6
immunological:
- acute haemolytic transfusion reaction (ABO incompatibility)
- allergic/anaphylactic reaction
- TRALI (transfusion-related acute lung injury)
non-immunological:
- bacterial contamination
- TACO (transfusion associated circulatory overload)
- febrile non-haemolytic transfusion reaction
what are the possible delayed transfusion reactions (to a blood transfusion)? 4
immunological:
- transfusion-associated graft-versus-host disease (TA-GvHD)
- post transfusion purpura
non-immunological:
- transfusion transmitted infection (TTI) - viral/prion
- iron overload
what is the pathological process of an acute haemolytic reaction (ABO incompatibility)?
- haemolysis of RBCs
- > release of free Hb
- > deposition of Hb in the distal renal failure
- > stimulation of coagulation
- > microvascular thrombosis
- > stimulation of cytokine storm
- > scavenges NO resulting in generalised vasoconstriction
what are the signs and symptoms of an acute haemolytic reaction? 7
when do these symptoms occur?
- fever + chills
- back pain
- infusion pain
- chest pain
- hypotension/shock
- haemoglobinuria (may be 1st sign in anesthetised patients)
- increased bleeding (DIC)
- sense of ‘impending death’
severe reactions may occur early in the transfusion (within first 15 mins)
(milder reactions may occur later but usually before the end of the transfusion)
What is a delayed haemolytic reaction?
what are the clinical signs/symptoms of this? 3
what are the laboratory findings? 4
onset 3-14 days following RBC transfusion
- delayed haemolytic reaction is due to immune IgG antibodies against RBC antigens other than ABO
- the antibodies are formed AFTER the transfusion
clinical features:
- fatigue
- jaundice
- fever
laboratory findings:
- drob in Hb
- increased LDH (lactate dehydrogenase)
- increased indirect bilirubin
- positive antiglobulin test
what is the Coomb’s test?
what is it also known as?
rabbit antibodies to human IgG
(called: anti-human globulin (AHG))
they are used to detect IgG antibodies on RBCs
- so see if RBCs are being attacked by immune system (as in a post-transfusion haemolytic reaction)=
- get visible agglutination if there are IgG on RBCs when AHG is added
aka:
- anti-human globulin test (AHG)
- direct anti-globulin test (DAT)
what does TRALI stand for?
why does it occur?
what is the mechanism of the condition?
transfusion related acute lung injury
- DONOR has antibodies to RECIPIENT’S LEUCOCYTES
(nb almost always complicates transfusion of plasma rich components - ie platelets or fresh frozen plasma)
donor antibodies attack recipients leucocytes
- > activated leucocytes lodge in pulmonary capillaries
- > release substances that cause endothelial damage and capillary leak
when does TRALI occur?
what are the clinical signs of it?
sudden onset of ‘acute lung injury’ occuring within 6 hours of a transfusion
- hypoxia
- new bilateral chest x-ray infiltrates (consolidation)
- no evidence of volume overload (eg heart size is normal)
how do you confirm a diagnosis of TRALI?
- donor’s blood is tested for HLA and granulocyte antibodies
- recipient’s blood is tested for expression of neutrophil antigens
confirmation of diagnosis if:
- donor has antibodies against antigens that are expressed on recipient’s granulocytes
what is the treatment for TRALI?
if mild:
- supplementary oxygen therapy
if severe:
- mechanical ventilation and ICU support
nb there is no role for diuretics or corticosteroids
what does TACO stand for?
what are the:
- symptoms? 5
- signs? 2
transfusion-associated circulatory overload
symptoms:
- sudden dyspnoea (SOB)
- orthopnoea
- tachycardia
- hypertension
- hypoxaemia
signs:
- raised BP
- elevated jugular venous pulse
what are the risk factors for TACO? 5
- elderly
- small children
- patients with compromised left ventricular function
- increased volume of transfusion
- increased rate of transfusion
nb this is hugely unreported/unrecognised by clinicians (if you suspect it, hold transfusion, if just to check that it’s not bacterial infection or another more serious adverse effect)
what are the differences between the presentation and treatment of TACO + TRALI?
- type of blood component transfusion which causes it?
- affect on BP?
- affect on temp?
- do diuretics worsen or improve it?
- does fluid loading worsen or improve it?
Type of blood component transfused:
- TRALI: usually plasma
- TACO: any
BP:
- TRALI: often reduced
- TACO: often raised
temp:
- TRALI: often raised
- TACO: normal
diuretics:
- TRALI: worsens
- TACO: improves
fluid loading:
- TRALI: improves
- TACO: worsens
what are the two different types of allergic reaction to a blood transfusion?
how do they present?
urticarial rash (+/- wheeze)
- often not severe
- hypersensitivity to a ‘random’ protein (in donor’s blood)
anaphylaxis
- severe, life-threatening reaction soon after transfusion started
- wheeze/asthma
- increased pulse
- decreased BP (shock)
- laryngeal/facial oedema
what is a febrile non-haemolytic reaction (FNHTR)?
why does it occur?
how should it be managed?
during (or soon after) transfusion:
- fever, rise in temp >1degree (+/- shakes/rigors)
- +/- increased pulse
- unpleasant but not life threatening (it is self-limiting)
FNHTR are due to cytokines (or other biologically active molecules) that accumulate during storage of blood components
- discontinue transfusion until you exclude ‘wrong blood’ or bacterial infection
what are the primary and secondary aspects of haemostatic plug formation?
primary
= aggregation
—platelet aggregation -> clotting
secondary
= coagulation cascade
-> thrombin -> fibrin
both together –> haemostatic clot
how do platelets become activated?
normal platelets in flowing blood (w receptors on their surface)
- if blood contacts collagen then a protein in blood (von willebrands factor) binds to the collagen and to the platelets, creating a connection
- platelets are therefore adhered to damaged endothelium and undergo ACTIVATION
–> aggregation of platelets into a thrombus (due to fibrinogen acting as a bridge between platelets)
what activates:
- the intrinsic clotting pathway?
- the extrinsic clotting pathway?
intrinsic:
- when blood exposed to COLLAGEN (from damaged surfaces)
extrinsic:
- when blood exposed to TISSUE FACTOR (released from tissues when endothelium is damaged)
what part of the coagulation cascade do these times measure:
- activated partial thromboplastin time?
- prothrombin time?
- thrombin clotting time?
activated partial thromboplastin time:
- intrinsic pathway
prothrombin time:
- extrinsic pathway
thrombin clotting time:
- common pathway
“intrinsic pathway is activated by contact with collagen, which is a bit like PLASTIC, thromboPLASTIN”
what factors are vitamin K dependent:
- clotting? 5
- anti-clotting? 2
clotting:
- factor 2
- factor 7
- factor 9
- factor 10
- prothrombin
anticlotting:
- protein c
- protein s
what are the procoagulant (2) and anti-coagulant (4) components found in the blood?
procoagulant:
- platelets
- clotting factors
coagulant:
- protein C
- protein S
- anti-thrombin III
- fibrinolytic system
what sort of bleeding do these types of bleeding disorders tend to cause:
- platelet/vessel wall defect?
- coagulation defect?
platelet/vessel wall defect:
- mucosal + skin bleeding
coagulation defect:
- deep muscular + joint bleeds
- bleeding following trauma
what is the general role of alpha and dense granules in platelets
contain chemicals which are released of platelet activation
these chemicals stimulate the activation and aggregation of other platelets
so a positive feedback loop
what does aspirin inhibit the synthesis of?
inhibits the synthesis of thromboxane (via inhibition of COX enzyme)
thromoxane is a hormone that is released from blood platelets, which induces platelet aggregation and arterial constriction
where is tissue factor (TF) found?
TF is a transmembrane receptor expressed by cells surrounding blood vessels
what does tissue factor activate?
factor 7 -> factor 7a
extrinsic pathway
which is faster: extrinsic or intrinsic pathway?
extrinsic (fewer steps)
what does factor 12 deficiency cause?
- prolonged clotting time in vitro
- but very rarely causes clinical symptoms
what bleeding disorders are caused by:
- factor 8 deficiency?
- factor 9 deficiency?
factor 8 = haemophillia A
factor 9 = haemophillia B
“A is earlier in the alphabet than B”
what is the end product of the fibrinolytic cascade?
what does this do?
plasmin (produced from plasminogen, which is converted by t-pa)
(t-pa = tissue plasminogen activator)
plasmin breaks down fibrin clot
what are the 4 broad different types of platelet/vessel wall defects which all give rise to a prolonged bleeding time? (each with an example)
1) reduced no. of platelets (thrombocytopenia)
- many causes (eg viruses, chemo)
2) abnormal platelet function
- eg aspirin/other drugs
3) abnormal vessel wall (rarer)
- eg ehlers danlos syndrome
4) abnormal intercation between platelets + vessel wall
- eg von willebrand diseas
what is an example of an acquired condition which causes abnormal vessel walls?
scurvy
what are petechiae?
red or purple spots on the skin, caused by a minor bleed from broken capillary blood vessels
they are NON-BLANCHING
what is the classical presentation of vascular/platelet defects?
- petechiae + superficial bruises
- affects skin + mucosal membranes
- spontaneous
- bleeding immediate, prolonged + NON-recurrent
what is the classical presentation of coagulation defects?
- deep spreading haematomas
- haemarthrosis
- retroperitoneal bleeding
- bleeding preolonged and often RECUURENT
what is haemarthrosis?
bleeding into joints
what is the scientific name for nose bleeds
epistaxis
what is the most common inherited bleeding disorder?
von Willebrand disease
what are the 2 functions of von willebrand factor?
- to bind platelets to wound site (esp collagen)
- to act as a carrier of factor 8
what are the 3 types of von willebrand disease?
type 1
- vWF is normal but there’s not enough of it
- less severe
- most common (75%)
type 2
- vWF is abnormal (not as effective) but there is enough of it
- less severe
- about 20% of cases
type 3
- there is very little vWF in blood
- severe
- very rare
what other condition can vWD present similar to? why?
mild haemophillia
as vWF carries factor 8 in the blood plasma so if there is less vWF then this can lead to low levels iof factor 8
what is the inheritance pattern of von Willebrand disease?
mainly autosomal dominant
nb penetrance is very variable though, even within families
what part of haemostasis is affected in von willebrands disease?
defective primary haemostasis
ie platelets/cell walls NOT coagulation
what other things (except vWD) can affect a person’s level of vWF?
increase? 3
decrease? 1
increase:
- illness
- stress
- exercise
decrease
- being blood group O
what are women with vWD given to reduce their menorrhagia?
combined oral contraceptive pill (COCP)
when are treatments normally given for von Willebrand disease?
- when symptoms occur
- before surgery
- during pregnancy
what anti-fibrinolytic treatment is given to treat vWD?
how does it work?
tranexamic acid
bind to plasminogen or plasmin. This prevents plasmin from binding to and degrading fibrin and preserves the framework of fibrin’s matrix structure
what other treatment is occasionally given to patients with vWD? (esp type 1)
what does it do?
desmopresin (aka DDAVP)
(it is an analogue of endogenous vasopressin)
- one of its actions is to release stores of vWF in endothelial cells
- only works temporarily
- side effect is water retension
- efficacy reduces after repeated uses
what vaccinations are people with vWD given? why?
hepatitis
because they are sometimes given (donated) plasma-derived concentrates containing vWF + so at higher risk from infected blood donors
what are the two most common hereditary COAGULATION deficiencies?
Haemophilia A + B
which coagulation screening test is elongated in haemophilia? why?
activated partial thromboplastin time (APTT)
as this measures the INTRINSIC pathway - where factor 8 + 9 are
what is the function of factor 13?
what does deficiency present as?
what do coagulation screening tests show?
to crosslink fibrin, stabilises clots
Bleeding tendencies similar to hemophiliacs develop, such as hemarthroses and deep tissue bleeding.
ALL NORMAL (APTT, PT, TCT) - as these measure formation of fibrin clots whereas factor 13 is to do with stabilisation of clots
why might some female carriers of haemophilia be more symptomatic than others?
due to random X-inactivation (lyonisation)
- if more X with normal gene is inactivated then factor 8 levels will be lower than 50% so mild symptoms may occur
what is the inheritance pattern of haemophilia A + B?
X-linked recessive
nb severity levels vary BUT are consistent between family members
about 30% of haemophilia cases are new mutations
what are the definitions of the three degrees of haemophilia severity?
factor 8 or 9 levels:
- mild = 6-50%
- moderate = 1-5%
- severe = <1%
nb mild haemophiliacs will only bleed during truma and surgery, whereas severe haemophiliacs will have lots of spontaneous bleeds
the more severe the condition, the earlier in life patients will present
what types of bleed do haemophiliacs tend to get? 5
- spontaneous/post traumatic
- haemarthrosis (joint bleeding)
- muscle haemorrhage
- soft tissue bleeds
- life threatening bleeds
what is haemophilic arthropathy?
what can reduce risk?
permanent joint disease occurring in haemophilia sufferers as a long-term consequence of repeated haemarthrosis
factor injections every other day, reduce number of joint bleeds so likelihood of permanent joint damage
what is the main treatment for haemophilia?
injections (every other day) of RECOMBINANT factor 8 or 9
nb factors from donated blood products no longer used
what are the 2 main complications of haemophilia treatment?
transfusion transmitted infections
- many adults got these before use of recombinant factors was used
- eg hepatitis, HIV, parvovirus
inhibitor development
- sometimes body can produce antibodies to injected factors
- more common in haemophilia A (25% of patients)
- means normal treatment is not effective
- more commonly temporary but can be permanent
what are the 6 most common causes of acquired bleeding disorders?
- vit K deficiency
- liver disease
- massive transfusion syndrome
- disseminated intravascular coagulation (DIC)
- iatrogenic causes
- acquired inhibitors (of coagulation)
what are the most important questions to ask when assessing someone with a possible bleeding disorder?
- date of onset/previous bleeding episodes?
- responses to ‘challenges’ (ie did surgery/dental extraction cause lots of bleeding) (nb in infants use things like bleeding from umbilical stump, vaccinations, circumcision)
- have they ever needed medical/surgical intervention to stop bleeding?
- any systemic illness? (eg liver problems)
- drug history?
- family history?
if the APPT (activated partial thromboplastin time) is prolonged, how can you tell if this is due to a deficiency of a factor or an inhibitor of the factor?
repeat test but mix patient’s plasma with plasma which you know has correct factors in, if:
- correction of APPT then: deficiency in patient’s plasma
- no correction of APPT then: presence of inhibitorin patient’s plasma
In liver disease, what results will be seen in these tests:
- platelet count?
- prothrombin time?
- APPT (activated partial thromboplastin time)?
- thrombin time?
platelet count:
- low
prothrombin time:
- prolonged
APPT:
- prolonged
thrombin time:
- normal
in DIC, what results will be seen in these tests:
- platelet count?
- prothrombin time?
- APPT (activated partial thromboplastin time)?
- thrombin time?
platelet count:
- low
prothrombin time:
- prolonged
APPT:
- prolonged
thrombin time:
- grosssly prolonged
“basically everything is shit, DIC is shit!”
in Massive transfusion syndrome, what results will be seen in these tests:
- platelet count?
- prothrombin time?
- APPT (activated partial thromboplastin time)?
- thrombin time?
platelet count:
- low
prothrombin time:
- prolonged
APPT:
- prolonged
thrombin time:
- normal
in oral anticoagulants (eg warfarin), what results will be seen in these tests:
- platelet count?
- prothrombin time?
- APPT (activated partial thromboplastin time)?
- thrombin time?
what other condition can cause these results?
platelet count:
- normal
prothrombin time:
- grossly prolonged
APPT:
- prolonged
thrombin time:
- normal
vit K deficiency
why do you get low platelet count in liver disease?
because liver problems often cause portal hypertension which backs into spleen, so platelets get trapped and clogged up in spleen, so have lower levels circulating (ie due to hypersplenism)
what is the action of warfarin?
warfarin is a vitamin K reductase inhibitor
- it stops vit k being recycled
vit K is needed in the activation of some coagulation factors
what are the 4 main causes of vit K deficiency? (not including warfarin treatment)
what are the mechanisms?
obstructive jaundice
- need bile to breakdown + absorb fat, vit K is a fat soluble vitamin -> deficiency
PROLONGED nutritional deficiency
- less fat for vit K to be absorbed in
broad spectrum antibiotics
- kill off gut flora
- a lot of out vit k is synthesised by gut flora
neonates (classic 1-7 days)
- all babies are given a vit k injection at birth to prevent this (aka haemorrhagic disease of the newborn)
why might patients on ICU be at higher risk of becoming vit K deficient?
have prolonged nutritional deficiency AND often lots of antibiotics
what coagulation factors are synthesised in the liver?
all except factor 8
what is a major cause of mortality in patients with liver disease?
cirrhotic coagulopathy
- complex reduction in coagulation factors, anti-coagulation factors + platelets leads to reduction in haemostatic abilities
- less likely to get spontaneous bleeds but highly likely to bleed a lot during surgery etc
- very hard to treat effectively
what is the definition of a ‘massive transfusion’
transfusion of a volume of blood equal to:
- patient’s total blood volume in <24hrs
OR
- 50% of patient’s blood volume within 3 hours
why do you get coagulation deficits with massive transfusions? (massive transfusion syndrome)
- due to RELATIVE (/dilutional) depletion of platelets + coagulation factors (as only RBC’s are transfused)
nb give fresh frozen plasma (FFP) as well to prevent this
also, less commonly, due to:
- DIC
- underlying disease (eg liver/renal drug treatment or surgery)
what are the main causes of ACUTE DIC? 5
what is this more likely to present as?
- sepsis (most common)
- obstetric complications
- trauma/tissue necrosis
- acute intravascular haemolysis (eg ABO incompatibilty blood transfusion)
- fulminant (aka acute) liver disease
bleeding as main symptom
what are the main causes of CHRONIC DIC? 4
what is this more likely to present as?
- malignancy
- end stage liver disease
- severe localised intravascular coagulation
- obstetric: retained dead foetus
end organ damage (due to microvascular clots) is main symptom