This document discusses microangiopathic haemolytic anaemia (MAHA) and disseminated intravascular coagulation (DIC). MAHA is haemolytic anaemia related to red blood cell fragmentation in small blood vessels. DIC is an acquired syndrome characterized by systemic activation of blood coagulation leading to microvascular thrombi in organs and multi-organ failure. DIC is secondary to triggers like sepsis, trauma, tumors, and obstetric complications. It involves initiation of fibrin deposition via tissue factor and impaired fibrinolysis. Diagnosis requires an underlying condition and laboratory abnormalities of platelets, coagulation factors, and schistocytes. Treatment focuses on the cause as well as replacing platelets, coagulation factors, and

1. MicroangiopathicMicroangiopathic
Haemolytic AnaemiaHaemolytic Anaemia
(MAHA)(MAHA)

2. MAHAMAHA
 Microangiopathic haemolytic anaemiaMicroangiopathic haemolytic anaemia (MAHA)“ is(MAHA)“ is
used to designate anyused to designate any haemolytic anaemiahaemolytic anaemia related torelated to
RBC fragmentation, occurring in associationRBC fragmentation, occurring in association
with small vessel disease. In DIC, RBCwith small vessel disease. In DIC, RBC
fragmentation is thought to result from thefragmentation is thought to result from the
deposition of fibrin or platelets within thedeposition of fibrin or platelets within the
microvasculaturemicrovasculature

3. Disseminated IntravascularDisseminated Intravascular
CoagulationCoagulation
DIC is an acquiredDIC is an acquired
syndrome characterized bysyndrome characterized by
the systemic activation ofthe systemic activation of
blood coagulationblood coagulation
generation of intravasculargeneration of intravascular
thrombin and fibrin.thrombin and fibrin.
Leads to microvascularLeads to microvascular
thrombi in various organsthrombi in various organs
contributing to multi-organcontributing to multi-organ
failure.failure.

4. Disseminated IntravascularDisseminated Intravascular
CoagulationCoagulation
 DIC is not a primary disease, but secondary to numerousDIC is not a primary disease, but secondary to numerous
triggering eventstriggering events
 Develop via 1 of the 2 pathways;Develop via 1 of the 2 pathways;
1) A systemic inflammatory response, leading to the1) A systemic inflammatory response, leading to the
activation of the cytokine network and subsequentactivation of the cytokine network and subsequent activationactivation
of coagulation via the extrinsic pathway (egof coagulation via the extrinsic pathway (eg sepsis)sepsis)
2)Release of procoagulant material into the bloodstream2)Release of procoagulant material into the bloodstream (eg.(eg.
Solid tumours, obstetric cases)Solid tumours, obstetric cases)
 In some situations (eg. Trauma and acute pancreatitis) bothIn some situations (eg. Trauma and acute pancreatitis) both
pathways may be present.pathways may be present.

5. Etiology ~1% of hospital admission
Sepsis and severe Infection (31%-43%) Bacterial infection
Toxins
Viral (HIV, CMV, VZV, hepatitis)
Fungal (invasive pulmonary aspergillosis)
Parasitic (malaria)
Rickettsial
Malignancy (24%-34%) Acute Promyelocytic Leukaemia
Solid tumours (e.g. breast, lung, prostate)
Obstetric Complication (4%-12%) Amniotic fluid embolism
Abruptio placentae
HELLP Syndrome
Eclampsia
Retained dead fetus syndrome
Massive Tissue Injury (1%-5%) Severe/major trauma
Burns
Extensive surgery
Systemic diseases (1%-5%) ABO transfusion incompatibility
Transplant rejections
Malignant hypertension
Vasculitis
Severe liver disease

6. DIC- common causesDIC- common causes
DIC occurs most often in the following clinical circumstances:DIC occurs most often in the following clinical circumstances:
 Complications of obstetrics-Placental tissue with tissue factorComplications of obstetrics-Placental tissue with tissue factor
activity enters or is exposed to the maternal circulation.activity enters or is exposed to the maternal circulation.
 Infection- Cell membrane components of microorganisms causeInfection- Cell membrane components of microorganisms cause
a generalized inflammatory response characterised by thea generalized inflammatory response characterised by the
systemic occurrence of pro-inflammatory cytokines.systemic occurrence of pro-inflammatory cytokines.
 Cancer- particularly mucin-secreting adenocarcinomas of theCancer- particularly mucin-secreting adenocarcinomas of the
pancreas, adenocarcinomas of the prostate, and acutepancreas, adenocarcinomas of the prostate, and acute
promyelocytic leukemia: Tumor cells express or release tissuepromyelocytic leukemia: Tumor cells express or release tissue
factor.factor.
 Shock due to any condition that causes ischemic tissue injury andShock due to any condition that causes ischemic tissue injury and
release of tissue factor.release of tissue factor.

7. Less common causes of DICLess common causes of DIC
 Severe tissue damage due to head trauma, burns, frostbite, orSevere tissue damage due to head trauma, burns, frostbite, or
gunshot woundsgunshot wounds
 Complications of prostate surgery that allow prostatic materialComplications of prostate surgery that allow prostatic material
with tissue factor activity (along with plasminogen activators) towith tissue factor activity (along with plasminogen activators) to
enter the circulationenter the circulation
 Enzymes in certain snake venoms that enter the circulation,Enzymes in certain snake venoms that enter the circulation,
activate one or several coagulation factors, and either generateactivate one or several coagulation factors, and either generate
thrombin or directly convert fibrinogen to fibrin.thrombin or directly convert fibrinogen to fibrin.
 Profound intravascular haemolysisProfound intravascular haemolysis
 Aortic aneurysms or cavernous hemangiomas (Kasabach-MerrittAortic aneurysms or cavernous hemangiomas (Kasabach-Merritt
syndrome) associated with vessel wall damage and blood stasis.syndrome) associated with vessel wall damage and blood stasis.

8. DIC-AcuteDIC-Acute
 Overt- occurs in short period of timeOvert- occurs in short period of time
 Thrombin produced in vast amounts triggeringThrombin produced in vast amounts triggering
coagulation and excess deposition ofcoagulation and excess deposition of
intravascular fibrinintravascular fibrin
 Results in severe bleeding and/or organ failureResults in severe bleeding and/or organ failure
 Seen in severe infection, obstetric complicationsSeen in severe infection, obstetric complications
and massive tissue injury due to trauma orand massive tissue injury due to trauma or
burns.burns.

9. Chronic DICChronic DIC
 Chronic DIC may develop when the body is exposed to smaller amounts ofChronic DIC may develop when the body is exposed to smaller amounts of
thrombin for prolonged periods (ie, solid tumours, retained products ofthrombin for prolonged periods (ie, solid tumours, retained products of
conception)conception)
 While coagulation factors and platelets are consumed, it is not as brisk as thatWhile coagulation factors and platelets are consumed, it is not as brisk as that
seen in acute DIC. The body is able to partially compensate throughseen in acute DIC. The body is able to partially compensate through
increased production of coagulation factors, platelets, antithrombin, andincreased production of coagulation factors, platelets, antithrombin, and
antiplasmin.antiplasmin.
 In addition, FDPs are still efficiently cleared by the liver. Therefore,In addition, FDPs are still efficiently cleared by the liver. Therefore,
thrombosis typically dominates bleeding in chronic DIC. Shock is often notthrombosis typically dominates bleeding in chronic DIC. Shock is often not
present.present.

10. PathophysiologyPathophysiology
 Initiation of fibrin deposition:Initiation of fibrin deposition:
Activation of coagulation cascade-Activation of coagulation cascade-
predominantly via the tissue factorpredominantly via the tissue factor
dependent pathway.dependent pathway.
 Amplification of fibrin deposition:Amplification of fibrin deposition:
Supressed anticoagulant pathwaysSupressed anticoagulant pathways
(↓anti-thrombin, ↓PC/PS and(↓anti-thrombin, ↓PC/PS and
↓tissue factor pathway inhibitor ).↓tissue factor pathway inhibitor ).
 Impaired fibrinolysis:Impaired fibrinolysis: Thrombin
causes release of PAI-1 from
endothelial cells and activates
thrombin-activatable fibrinolysis
inhibitor (TAFI) in the plasma, both
of which impair plasminogen
activation, thereby reducing clot
dissolution from plasmin.

11. DIC PathophysiologyDIC Pathophysiology

12. Pathophysiology- DIC in SepsisPathophysiology- DIC in Sepsis

13. Diagnosis of DICDiagnosis of DIC
 Diagnosis is only made in patients with anDiagnosis is only made in patients with an
underlying disorder known to be associated withunderlying disorder known to be associated with
DIC DIC in conjunctionin conjunction with laboratory abnormalities with laboratory abnormalities
(platelet count, coagulation profile, and fibrin(platelet count, coagulation profile, and fibrin
degradation marker, presence of schistocytes indegradation marker, presence of schistocytes in
peripheral blood film).peripheral blood film).

14. Peripheral PresentationPeripheral Presentation
 Schistocytes in PBSSchistocytes in PBS
 Thrombocytopenia-commonThrombocytopenia-common
laboratory diagnostic featurelaboratory diagnostic feature
of DIC (93% of cases). Inof DIC (93% of cases). In
many cases of DIC, themany cases of DIC, the
thrombocytopenia may notthrombocytopenia may not
be severe. Note downwardbe severe. Note downward
trend in the platelet counttrend in the platelet count
even if the recent counteven if the recent count
remains in the normal rangeremains in the normal range

15. Case StudyCase Study
75 year old female. History of renal and splenic infarct75 year old female. History of renal and splenic infarct..
17/7/18 18/7/18 19/07/18
Hb 84 83 83
RCC 2.87 2.86 2.85
PCV .262 .259 .260
MCHC 320 320 320
MCH 29 29 29
RDW 16 16 17
PLT 147 112 88
PT 81.1 89.5
INR 7.0 7.7
APTT 85 72
TCT 24 22
Fibrinogen 0.3 0.3
DDimmer 40.440.4

16. Treatment of DICTreatment of DIC
 Acute-Treatment includes correction of theAcute-Treatment includes correction of the
cause and replacement of platelets,cause and replacement of platelets,
coagulation factors (in fresh frozen plasma),coagulation factors (in fresh frozen plasma),
and fibrinogen (in cryoprecipitate) to controland fibrinogen (in cryoprecipitate) to control
severe bleeding. severe bleeding.
 Chronic-Heparin is used as therapy (orChronic-Heparin is used as therapy (or
prophylaxis) in patients with slowly evolvingprophylaxis) in patients with slowly evolving
DIC who have (or are at risk of) venousDIC who have (or are at risk of) venous
thromboembolism.thromboembolism.

17. Blood Component Therapy in DisseminatedBlood Component Therapy in Disseminated
Intravascular CoagulationIntravascular Coagulation
Fresh frozen plasmaFresh frozen plasma
 When there is bleeding and abnormal coagulationWhen there is bleeding and abnormal coagulation
 Usually 4 units (10–15 mL/kg) are rapidly infusedUsually 4 units (10–15 mL/kg) are rapidly infused
 Is not indicated for chronic DICIs not indicated for chronic DIC
CryoprecipitateCryoprecipitate
 This contains fibrinogen in a concentrated formThis contains fibrinogen in a concentrated form
 May be indicated at fibrinogen levels lower than 1.0 g/L and where there is clinicalMay be indicated at fibrinogen levels lower than 1.0 g/L and where there is clinical
bleedingbleeding
 Use to keep fibrinogen levels above 1.0 g/LUse to keep fibrinogen levels above 1.0 g/L
PlateletsPlatelets
 May be appropriate when clinical bleeding and thrombocytopenia are consideredMay be appropriate when clinical bleeding and thrombocytopenia are considered
major contributory factorsmajor contributory factors

Thrombotrol-VFThrombotrol-VF
 Antithrombin (Thrombotrol-VF) replacement have also been used in some patientsAntithrombin (Thrombotrol-VF) replacement have also been used in some patients
 May have a role in the managementMay have a role in the management of those patients who do not respond to simpleof those patients who do not respond to simple
replacement therapy of blood componentsreplacement therapy of blood components

18. Other forms of MAHA-TTPOther forms of MAHA-TTP
Thrombotic Thrombocytopenic PurpuraThrombotic Thrombocytopenic Purpura
 Acquired thrombotic thrombocytopenic purpura (TTP) is aAcquired thrombotic thrombocytopenic purpura (TTP) is a
condition in which there is a decrease in the proteolyticcondition in which there is a decrease in the proteolytic
activity of the von Willebrand factor (vWF) cleaving proteaseactivity of the von Willebrand factor (vWF) cleaving protease
enzyme, ADAMTS13 in the plasma.enzyme, ADAMTS13 in the plasma.
 Due to the decrease in ADAMTS13 activity, when vWF isDue to the decrease in ADAMTS13 activity, when vWF is
released from endothelial cells, it is not broken down to itsreleased from endothelial cells, it is not broken down to its
smaller functional form.smaller functional form.
 These larger vWF multimers cause platelets to aggregateThese larger vWF multimers cause platelets to aggregate
throughout the vasculaturethroughout the vasculature diffuse platelet thrombidiffuse platelet thrombi
formation, ischemia of the affected organs, and a severelyformation, ischemia of the affected organs, and a severely
decreased platelet count.decreased platelet count.
 Coagulation factors are not consumed so that the PT andCoagulation factors are not consumed so that the PT and
PTT remain normal.PTT remain normal.

19. TTPTTP

20. Other forms of MAHA- HUSOther forms of MAHA- HUS
 Typical hemolytic uremic syndrome (HUS) isTypical hemolytic uremic syndrome (HUS) is
caused by caused by Escherichia coliEscherichia coli Shiga toxin. Shiga toxin.
 The toxin that is produced can cause direct cellThe toxin that is produced can cause direct cell
damage to the renal microvasculature, the GIdamage to the renal microvasculature, the GI
tract, and other organ systems.tract, and other organ systems.
 Presentation includes a history of diarrhoea,Presentation includes a history of diarrhoea,
acute kidney injury, and severeacute kidney injury, and severe
thrombocytopenia.thrombocytopenia.
 Typical HUS is more commonly found inTypical HUS is more commonly found in
childrenchildren but does occur in adults. but does occur in adults.

21. Other forms of MAHA- atypical HUSOther forms of MAHA- atypical HUS
 Another form of HUS is atypical HUS (aHUS).Another form of HUS is atypical HUS (aHUS).
It is caused by a genetic predilection where aIt is caused by a genetic predilection where a
decrease in the production of complementdecrease in the production of complement
inhibitors occurs when the patient is exposed toinhibitors occurs when the patient is exposed to
stressful stimuli.stressful stimuli.
 Leads uncontrolled complement activation withLeads uncontrolled complement activation with
direct endothelial cell damage in the kidney, GIdirect endothelial cell damage in the kidney, GI
tract, and other organ systems.tract, and other organ systems.

24. MAHA-DifferentialsMAHA-Differentials