Transcript IMPLICATIONS OF THROMBOSIS IN SOLID VERSUS …

Management and Care of
Dengue with Bleeding
Dr. Bahariah binti Khalid
Head Unit
Internal Medicine & Clinical Hematology
Faculty of Medicine and Health Sciences
Universiti Putra Malaysia
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Outline
1. Overt and Assumptions of bleeding
2. Points to be emphasized to the team dealing
with bleeding dengue
3. Dilemmas of blood product transfusion in
bleeding dengue
4. Challenges that clinicians have to expect
because it is real.
Table 2. Clinical symptoms experienced by study population.
Rathakrishnan A, Wang SM, Hu Y, Khan AM, et al. (2012) Cytokine Expression Profile of Dengue Patients at Different Phases of Illness.
PLoS ONE 7(12): e52215. doi:10.1371/journal.pone.0052215
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052215
Table 1. Demographics of study cohort.
Rathakrishnan A, Wang SM, Hu Y, Khan AM, et al. (2012) Cytokine Expression Profile of Dengue Patients at Different
Phases of Illness. PLoS ONE 7(12): e52215. doi:10.1371/journal.pone.0052215
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052215
Table 2. Clinical symptoms experienced by study population.
Rathakrishnan A, Wang SM, Hu Y, Khan AM, et al. (2012) Cytokine Expression Profile of Dengue Patients at Different
Phases of Illness. PLoS ONE 7(12): e52215. doi:10.1371/journal.pone.0052215
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052215
Table 3. Liver enzyme profile of study population.
Rathakrishnan A, Wang SM, Hu Y, Khan AM, et al. (2012) Cytokine Expression Profile of Dengue Patients at Different Phases of Illness.
PLoS ONE 7(12): e52215. doi:10.1371/journal.pone.0052215
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052215
FBC in DHF
 High hematocrit
 Low white blood cells count
 Low absolute neutrophils
 High absolute lymphocytes
 High atypical lymphocytes
 Low platelets
 Slightly prolonged PT and APTT
 Slightly prolonged or normalized thrombin
time
Table 4. Blood and white blood cells profile of study population.
Rathakrishnan A, Wang SM, Hu Y, Khan AM, et al. (2012) Cytokine Expression Profile of Dengue Patients at Different Phases of Illness.
PLoS ONE 7(12): e52215. doi:10.1371/journal.pone.0052215
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052215
Table 5. Laboratory diagnostic assay results in the study cohort.
Rathakrishnan A, Wang SM, Hu Y, Khan AM, et al. (2012) Cytokine Expression Profile of Dengue Patients at Different Phases of Illness.
PLoS ONE 7(12): e52215. doi:10.1371/journal.pone.0052215
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052215
Table 7. Association of cytokines with clinical parameters in the study cohort.
Rathakrishnan A, Wang SM, Hu Y, Khan AM, et al. (2012) Cytokine Expression Profile of Dengue Patients at Different
Phases of Illness. PLoS ONE 7(12): e52215. doi:10.1371/journal.pone.0052215
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052215
Plasma leakage
The cause of bleeding Dengue it is hemostasis defect
Overt and Assumptions of bleeding
1. Understanding haemostasis
2. Take a good bleeding history
3. Understand the possible causes for
deranged coagulation profiles
4. Investigate the cause of a significant
bleeding history and prolonged clotting
times
5. Managing coagulopathy
Overt and Assumptions of bleeding
 Immediate bleeding
 Defects

in primary haemostasis
- low platelets, CVC
 Vascular

abnormality
-capillary leak, procedures
 Delayed bleeding
 Defects
in secondary haemostasis
Dengue infection can lead to disseminated
intravascular coagulation.
A. Disagree
B. Disagree Somewhat
C. Neutral
D. Agree Somewhat
E. Agree
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Massive transfusions can lead to
disseminated intravascular coagulation.
A. Disagree
B. Disagree Somewhat
C. Neutral
D. Agree Somewhat
E. Agree
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A good bleeding history is the
best screening tool.
Parameters to indicate risk of bleeding in
general…but in dengue?
Age > 85
Active gastroduodenal ulcer
Bleeding in 3 months before admission
Central Venous Line insertion
Current cancer
Hepatic failure ( INR 1.5 )
ICU / CCU admission
Male sex
Platelet count < 50x 10˄9/L
Rheumatic disease
Severe renal failure
(GFR , 30 mL/min/m²)
WHO Bleeding Grades
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Grade 0, none
Grade 1, petechiae, ecchymosis, occult
blood in body secretions, and mild vaginal
spotting
Grade 2, evidence of gross hemorrhage not
requiring red cell transfusions over routine
transfusion needs (e.g. epistaxis,
hematuria, hematemesis)
Grade 3, hemorrhage requiring transfusion
of 1 or more units of red cells/day
Grade 4, life-threatening hemorrhage,
defined as massive bleeding causing
hemodynamic compromise or bleeding into
a vital organ (e.g., intracranial, pericardial,
or pulmonary hemorrhage)
Tail it to your individual patient
A significant bleeding history
 Epistaxis not stopped by 10 mins compression
or requiring medical attention
 Cutaneous haemorrhage or bruising without
apparent trauma (esp. multiple/ large)
 Prolonged (>15 mins) bleeding from trivial
wounds, or in oral cavity or recurring
spontaneously within 7 days
 Post-operative bleeding
 Menorrhagia (esp. from menarche)
Bleeding in the hospitalized patient
 Bleeding prolonged, delayed or recurrent; or
more rapid than normal?
 Single site or several sites?
 Appropriate to injury?
 Past h/o bleeding?
 Medications?
 Diseases?
 Family history?
Case
 35/M/lady D5 of fever admitted DSS with AKI on Noradrenaline.
 She was covered with broad spectrum antibiotics.
 Her GCS and saturation dropped that she requires ventilatory support
and admitted to ICU. CT brain shows no ICB.
 3 hours later she had bleeding from the oral cavity and nose but no
other bleeding elsewhere. The suction tube measured 1L .
 Hb 10.1 HCT37 TWC 6.9 Plt 32 Pt 14 APTT 50
Will you request Sr. Fibrinogen for this
patient?
A. Disagree
B. Disagree Somewhat
C. Neutral
D. Agree Somewhat
E. Agree
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Should DIVC regime be given?
A. Disagree
B. Disagree Somewhat
C. Neutral
D. Agree Somewhat
E. Agree
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There is no FIXED DIVC regime
Outline
1. Overt and Assumptions of bleeding
2. Points to be emphasized to the team dealing
with bleeding dengue
3. Dilemmas of blood product transfusion in
bleeding dengue
4. Challenges that clinicians have to expect
because it is real.
In critical care medicine
In critical care medicine
Case
 35/M/lady D5 of fever admitted DSS with AKI on Noradrenaline.
 She was covered with broad spectrum antibiotics.
 At 36 hours of defervescence, her GCS and saturation dropped that
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she requires ventilatory support and admitted to ICU. CT brain shows
no ICB.
3 hours later she had bleeding from the oral cavity and nose but no
other bleeding elsewhere. The suction tube measured 1L .
Hb 10.1 HCT37 TWC 6.9 Plt 32 Pt 14 APTT 50
Other parameters were normal
The volume partly because of the suction water for irrigation
Does this patient needs blood product
transfusion?
A. Disagree
B. Disagree Somewhat
C. Neutral
D. Agree Somewhat
E. Agree
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Are prophylactic platelet
transfusions necessary?
 Unresolved issue
 Should we give it before bleeding or only with
the onset of active bleeding?
 Might be safe in a select group of patients
Platelet Transfusion
 At least 7.1 x 109 platelets/L are
consumed daily in endothelial support
functions
 The equivalent of approximately one
Random Donor Platelet daily for a 70 kg
adult with marrow failure
Kerok
Petecheal
hemorrhages
Purpura fulminans
Therapeutic Platelet Transfusion
 Platelet transfusion is usually needed when
WHO bleeding grade 2 or more
 Grade 3 or 4 Bleeding is usually associated
with other factors (not low platelets alone)
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Uraemia
Drugs
Ulcers
Bleeding tumours
Platelets : 2 types
Random blood donor(RDP):
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Collected from whole blood
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Expected increment per unit:
5-7 x109/L
○
Should contain ≥5.5 x 1010
platelets (average content
Single donor apheresis(SDP):
○ Collected from apheresis by
automated instrumentation
○ Expected increment per unit: 30
- 50 x109/L
○ Should contain ≥3.0 x 1011
approximately 8.0 x 1010) per
platelets (average content
bag in approximately 50 mL
approximately 3.5-4.0 x 1011)
of plasma.
per bag in about 250 mL of
plasma
Judiciously
RDP
Advantage- ?
Disadvantage- exposure to
many donor viral and
bacterial transmission,
many donor allosensitization
SDP
Advantage- single donor
exposure
Disadvantage- expensive –
RM300, more volume
(equivalent to 4-6 random
donor)
Response
 Measure platelet count from 10 minutes to 3
hours after transfusion.
 Generally, expect an adult platelet count
increment of approximately 7-10,000/ mm3
for each RDP given, or 30-60,000/ mm3 for
each SDP given.
Indication
 Use to treat bleeding due to critically decreased
circulating platelet counts or functionally
abnormal platelets.
 Use prophylactically to prevent bleeding at prespecified low platelet counts.
 Maintain platelet count
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>10,000/mm3 in stable, non-bleeding patients,
>20,000/mm3 in unstable non-bleeding patients
and
>50,000/mm3 in patients undergoing invasive
procedures or actively bleeding.
Platelets is contraindicated in
Immune-mediated platelet destruction
 HIT/ITP- Such use is usually reserved for
situations of potentially life-threatening
haemorrhage
Thrombotic thrombocytopenic
purpura/haemolytic uraemic syndrome
 Transfusion of platelets has been accompanied
by acute deterioration
 Still allowable for large bore cannulation
Fresh Frozen Plasma (FFP)
 Plasma consists of the noncellular portion of
blood that is separated and frozen after
donation prepared from whole blood or
collected by apheresis
 Stored at –30°C
 Plasma frozen within 8 hours is called fresh
frozen plasma (FFP)
 1 unit FFP (150 – 300 ml), will increase each
clotting factor activity by 2-3%
Indications
Frozen Plasma is indicated for use in patients with the following
conditions:
1. Active bleeding due to deficiency of multiple coagulation
factors, or risk of bleeding due to deficiency of multiple
coagulation factors.
2. Severe bleeding due to warfarin therapy, or urgent reversal of
warfarin effect
3. Massive transfusion with coagulopathic bleeding.
4. Bleeding or prophylaxis of bleeding for a known single
coagulation factor deficiency for which no concentrate is
available.
5. Thrombotic thrombocytopenic purpura.
6. Rare specific plasma protein deficiencies, such as C1-inhibitor.
and contraindications of FFP
 Frozen Plasma should not be used for
1. Increasing blood volume or albumin concentration
2. Coagulopathy that can be corrected with administration of
Vitamin K.
3. Normalizing abnormal coagulation screen results, in the
absence of bleeding.
Dosing
 Determined by the patient size and clinical condition.
 For correction multiple coagulation factor deficiencies, plasma
transfusion should be guided by coagulation testing.
 Therapeutic or prophylactic replacement
 PT > 1.5 times the mid-range of normal
 APTT > 1.5 times the top of the normal range
 or factor assay less than 25% in an appropriate clinical setting.
 If testing not readily available, use clinical evidence of bleeding for
transfusion decisions.
 Dosing guide
 achieve a minimum of 30% of plasma factor concentration eg.
10-20 mL/kg, though more may be required depending upon
the clinical situation.
 12–15 ml/kg (usually about 3-6 units) in would typically increase
fibrinogen levels by about 1 g/l
Lactate >5, I would choose whole blood to be
transfused?
A. Disagree
B. Disagree Somewhat
C. Neutral
D. Agree Somewhat
E. Agree
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Whole blood
 Massive transfusion guideline
 Short Screening at least 2 days as PDN are
tight at infective screening.
 More likely for allosensitization as they have
more Lymphocytes
 High 2,3,DPG
 Equivalent to 1 FFP, 1 unit RDP, 1 pint PC
Transfusion reactions
Outline
1. Overt and Assumptions of bleeding
2. Points to be emphasized to the team dealing
with bleeding dengue
3. Dilemmas of blood product transfusion in
bleeding dengue
4. Challenges that clinicians have to expect
because it is real.
Dengue fever are taught as
mostly not septic looking.
 Can this cause late in instituting treatment for
sepsis thus high mortality?
 Survival Sepsis guideline has transfusion
guideline that helps just as a guide.
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Is dengue Sepsis?
 No studies on prevalence of dengue with
concomitant sepsis.
 Viraemia in the first 3-5 days (old school
considered as sepsis)
 Later part is the ADE responses
 Latest school- Sepsis is meant for
BACTERIAL only
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Outline
1. Overt and Assumptions of bleeding
2. Points to be emphasized to the team dealing
with bleeding dengue
3. Dilemmas of blood product transfusion in
bleeding dengue
4. Challenges that clinicians have to expect
because it is real.
Dengue in challenging population
 Foreigners and disabled-language barrier
 Concomittant other infections
 Dengue patients warfarinized or on NOAC
 Pregnancy and postpartum
 Obese
 Elderly
 Post vaccination
 Transfusion reactions
 Early institution of VTE prophylaxis in high
risk of thrombosis
Conclusion
 Difficult bleeding dengue is a challenge and it can
happen at all ages and it is due to defect in
hemostasis
 Emphasize should be made to identify dengue
population at risk of bleeding and the bleeding
sites as early when the patient is suspected to
have dengue infection
 Stop the bleeding or advise the managing team
accordingly to what is watchful expectation.
Conclusion
 Avoid hypothermia, hemodilution/overload,
acidosis and prolonged unsolved bleeding at all
times as it affects the poor function of the
coagulation factors.
 Find the alternative if failing the conventional
treatment but remember it is not without side
effects.