Approach to bleeding

disorders
By Dr kalkidan S ( ECCM R2)
Moderator: Dr Sharon Y. ( ECCMR3)
Advisor: Dr Woldesenbet W. ( assosciate professor of Emergency and Critical care
Medicine)
September 7, 2023
objective
• Understand the basic pathophysiology of bleeding disorders
• Describe the approach to the bleeding patient
• Mention investigation modalities and their use

• Identify common pathologies like TTP, DIC, ITP

outlines
• Introduction
• Approach to bleeding disorders
• Blood tests for coagulation disorders
• Indications for platelet transfusion
• DIC, TTP HUS clinical presentation and management
hemostasis
• A process involving maintenance of vessel integrity, formation of
platelet plug, propagation of coagulation cascade, clot development,
fibrinolysis, clot degradation

• Common hemostatic abnormalities are acquired, hepatic

insufficiency, iatrogenic less commonly congenital
Approach to the bleeding patient
• Most patients at the ED present with bleeding due to trauma with
normal hempostatic mechanisms
•
• When should we suspect abnormal bleeding?
• Spontaneous bleeding from multiple sites. Bleeding from
nontraumatized sites. Delayed bleeding several hours after the
trauma, bleeding to deep tissues or joints,
in the critically ill patients

Single center prospective study of 1328

patients: GI bleeding was the commonest
site, risk factors: MV, malnutrition, renal
History
• Prior bleeding events over time
• Outcome of bleeding challenges
• Menstrual history
• Pregnancy history
• Malabsorption syndromes causing nutritional deficiency
• Iron replacement supports
• Family history
• Medication use, underlying medical condition
Physical examination
• Petechiae, bruises(of different age), purpura
• Sites of bleeding: joint space
• Splenomegally
• Cardiac findings
Laboratory testing
• Prothrombin time: indicator of tissue factor( extrinsic pathway) and
common pathway

• INR: ration of observed prothrombin time to internationally validated

control prothrombin time
• INR allows valid comparison of anticoagulant effect of warfarin over
time and between laboratories
• Generally coagulation times when at least 50% depletion or inhibition
factors
• The PT doesn’t become prolonged until 10% or less of normal are
present
• Warfarin administration, vit K deficiency, liver disease, DIC, oral direct
thrombin and Xa inhibitors: dabigatran, rivaroxaban
• ~ heparin doesn’t affect the PT

Bc heparin binding chemical eliminates it effect

APTT
• Indicator of intrinsic and common pathway
• Its performed by the addition of non tissue factor thromboplastic
material and negatively charged particulate contact activator to
plasma
• factor VIII, IX, or XI, heparin administration, lupus anticoagulant
Thrombin time
• Measures the time to conversion of fibrinogen to fibrin
• Indicator of fibrin concentration
Activated whole blood clotting time
• Obtained by adding negatively charged particle to fresh whole blood
& measures the formation of clot
• Less sensitive to heparin thus used in the setting high heparin infusion
settings such as CABG, ECMO, PCI
Fibrin degradation products and D-dimer
• Show active fibrinolysis in patients with substantial intravascular clot
burden and DIC
• Trauma, sugery, hepatic disease, pregnancy, ca
Anti factor Xa activity
• Used to monitor the adequacy of anticoagulation in patients receiving
heparin, LMWH, rivaroxaban, apixaban
Thromboelastography
• Point of care assay
• Both platelet and soluble coagulation assays
• Provides information on coagulation and fibrinolysis
• Increasingly being used in critically ill patients to guide blood product
administration and indicator of severity of illness
• In surgery, cardiac surgery, prognostic indicators
• Primary and secondary hemostasis

• Platelet defects manifest with petechiea and mucosal bleeding

• Coagulation defects present as spontaneous or excessive hemorrhage
Interventions for the bleeding patient
• Platelet transfusion aim
• Acute life threatening bleeding, ICH
• Neurologic/ vascular surgery to maintain a conc of 100x109/L
• General surgical procedures, routine procedures 20-50,000
• Platelet transfusions are ineffective if the cause of thrombocytopenia
is enhanced destruction(ITP, DIC, drug induced thrombocytopenia,
sepsis)
FFP
• Contains all of the coagulant factors
• 10-15ml/kg
• For the correction of INR(>1.5-2X control)

• Risk of acute lung injury

cryopreciptate

• Fibrinogen, fibronectin, vonwillbrand factor, facor VIII, factorXIII

• Constructed in low volumes(10-15ml)
• Used for hypofibrinogenemia caused by diution, massive transfusion,
or consumptive coagulopathy
• Target level of fibrinogen above 100mg/dL
Others…
• Activated factor VII
• Tranexamic acid(cx in DIC, upper pole urinary bleeding)
• PCC
Acquired platelet defects
• Quantitative vs qualitative

• Non palpable petechial rash in dependent areas, mucosal bleeding,

menorrhagia, hemoptysis, hematuria, hemarthrosis

• Secure circulatory stability

Thrombocytopenia
 ITP

• Results from antibodies against platelet antigens

• Idiopathic thrombocytopenic purpura and autoimmune type
• Primary ITP
• Secondary ITP: pathogens, disease state, malignancy, drug induced
• HIV, hepatitis virus, EBV, varicella, rubella,
ITP
classification
In terms of duration
• Newly diagnosed(less than 3 month)
• Persistent(3-12 month)
• Chronic( over 12 month)
Causative factors
~Primary
~Secondary
ITP treatment
• Mainly supportive
• Corticosteroids when platelet count less than 30,000/mm3
• Dexamethasone 40mg po or IV daily for 4 days
• IVIG
• TPO-RA
• Splenectomy is a last resort
• Pediatric age group
disposition
• Admit newly diagnosed adult patients with platelet count of less than
20,000/mm3
• In pediatric age group: When there is uncertainty in the diagnosis and
followup
Drug induced ITP
• Quinine, quinidine : innocent bystander mechanism
• B-lactams, quinolones, digoxin, sulfonamides, phenytoin, Aspirin
usually within 24hrs of use
• It should improve after stoppage of the offending drug 1-2 days
• Consider corticosteroids, IVIG, possibly platelet transfusion
Drugs that impair platelet function or produce
thrombocytopenia
Heparin induced thrombocytopenia
• Heparin pairs with platelet factor 4, procoagulant substance found in
platelet granules
• Rapid generation of antibodies – thrombocytopenia , activate
platelets thus create hypercoagulability
• 33-50% will develop HIT with thrombosis
• HIT like reaction
• 0.1-7% risk, highest at 5 days, UFH & higher dose more risky
• Women, surgical, trauma patients
• Delayed HIT(14 days)
……4Ts scoring system
• Anti PF4 heparin enzyme immunoassay

• Manage the thrombotic condition

• Stop heparin
• Start non heparin anticoagulants: argatroban, DOAC
Drugs…
• Bleeding disorder related to heparin therapy can be reversed with
protamine sulfate
• 1mg of protamine sulfate for every 100 unit of hepari

• Risk benefit analysis should be done

• Dabigatran…. 5gm idracuzimab, a PCC, 4 pcc
• Apixaban/Rivaroxaban…… andexanet alfa, 4FPCC, aPCC
Thrombotic microangiopathies: TTP, HUS
• Defined by the simultaneous presence of thrombocytopenia and
intravascular hemolysis
TTP
• Results from autoantibodies to ADAMTS13
• Platelet aggregates, formation of microthrombi inducing tissue
ischemia, platelet consumption then MAHA

• HUS has more renal involvement, TTP more neurologic

• 90% in adulthood more common in women
• PLASMIC score for risk stratification
Other lab findings
• Schistocyes on peripheral blood smear, negative direct coombs test,
elevated LDH, anemia
• Raised creatinine

• What will happen to the PT, PTT, INR

Continued….
• Pentad of hemolysis, thrombocytopenia, neurologic defects, low
grade fever, renal dysfunction
• Present with abdominal pain, N/V, seizure, headache, fluctuating
neurologic defecits

• TTP like thrombotic microangiopathies ,

Treatment
• Patient may develop shock, respiratory failure and neurologic
deterioration

• Plasma exchange is indicated on daily basis till platelet is >150x109/L

• rituximab, high dose steroid, or splenectomy

• Predinsolone1mg/kg po/day

• Platelet transfusion only for life threatening condition

Coagulation disorders
Hemophilia A: deficiency of factor VIII
Prevalence: 17 per 100000 males and 1,125000 affected worldwide
• Occurs as disorder of secondary hemostasis
• Bleeding can occur in deep muscles, joints, urinary tracts intracranial
sites
• ICH is a major cause of death
• Recurrent hemrthrosis and joint destruction common cause of
morbidity
• Mucosal bleeding if VWD or platelet dysfunction
• Trauma may be the inciting event& patients will have delayed
bleeding for days to weeks
• Determine factor VIII level, blood type antihemophilic factor
antibodies
• Factor replacement therapy, desmopressin
DIC
• Acquired coagulopathy reflecting dysregulated coagulation and
fibrinolytic pathways
• Combined platelet and coagulation disorder

• Imbalance between procogulation and thrombotic process

pathogenesis
causes
• Bacterial sepsis(commonest cause) , viral, fungal sepsis
• Obstetric causes: abruption placenta amniotic fluid embolism
• Malignant disorders: adenocarcinoma, acute promyelocytic leukemia

• Trauma and tissue injury

• Vascular disorders, snake envenomation
• ARDS, shock, massive transfusion
• Diagnosis is made using clinical presentation, exclusion of other
causes and consistent lab findings
• Low platelet, prolonged PT, PTT, INR, elevated D-dimer

• TEG drawing, test should be repeated every 6-8hr

• Scoring systems: ISTH 91% sensitive and 96% specific

Chronic DIC
• Low grade compensated DIC
• in cases of giant hemangioma, metastatic ca or dead fetus syndrome
• Plasma levels of FDP or D-dimer elevated
• aPTT, PT, fibrinogen values within normal range or high
• Lower degree if red cell fragmentation
Treatment principles
• Treat the underlying cause
• Platelet transfusion when indicated
• FFP and cryoprecipitate with target INR and fibrinogen levels
• Heparin is used in those with clinically apparent thrombosis
•
• Heparin is used in purpura fulminans, low grade DIC in solid tumors,
during removal of dead fetus, surgical resection of giant
hemangiomas
• Tranexemic acid in trauma but generally contraindicated
Fibrinogen levels >150mg/dL PT no longer than 3s above
reference
Take home assignment
• Coagulopathy related with medication use
• Rare miscellaneous coagulobathies: inherited disorders
• Vonwillbrand factor disease
references
Ron M. Walls. (2023) Rosen’s emergency medicine concepts and clinical
practice. 10th edition. Philadelphia. Elsevier
Hall, Schmidt. (2015) Principles of Critical care. 4th edition. New York. McGraw
Hill
Judith E. Tintinalli. (2020) Tintinalli emergency medicine 10th edition New York.
McGraw Hill
Loscalo, Fauci, Kasper, Hauser, Longo, Jameson.(2022) Harrison’s principles of
internal medicine 21st edition. New York. McGraw Hill
John P greer. (2019) Wintrobe’s Clinical hematology 14th edition. Wolters
Kluwer. China
Uptodate, 2023. approach to the bleeding patient