Everything ablout HUS and TTP in pregnancy- reference Williams obstetrics and recent recommended updates

Your credits are exhausted. You can purchase a top-up or subscribe to a plan to continue using Orris. If you're already subscribed, your daily credits will reset tomorrow.

Everything ablout HUS and TTP in pregnancy- reference Williams obstetrics and recent recommended updates In simple languages and flowcharts

Reading File

Finding Sources

Searching PubMed

thrombotic thrombocytopenic purpura hemolytic uremic syndrome pregnancy

Finding Sources

Reading File

Finding Sources

Reading File

Finding Sources

Reading File

Reading Article

PMID: 38396391

Reading File

Reading Article

PMID: 37586700

Searching Images

thrombotic microangiopathy TTP HUS pathogenesis ADAMTS13 diagram pregnancy

A composite clinical image consisting of three panels illustrating a multi-organ manifestation of Thrombotic Thrombocytopenic Purpura (TTP). Panel A is an axial T2 FLAIR magnetic resonance image of the brain showing hyperintense signals in the left anterior cerebral artery (ACA) distribution, consistent with acute infarction, alongside chronic hypointense areas indicating prior infarcts. Panel B displays a two-dimensional trans-esophageal echocardiogram (TEE) focused on a prosthetic mitral valve; it reveals a 1.5 cm irregular, echogenic mass (vegetation) attached to the atrial surface, indicative of non-bacterial thrombotic endocarditis. Panel C shows a Wright-Giemsa stained peripheral blood smear at high power. The smear demonstrates microangiopathic hemolytic anemia characterized by prominent schistocytes (fragmented red blood cells), indicated by black arrows, against a background of normocytic erythrocytes. Together, these images teach the classic clinical triad of neurological deficits, cardiac involvement, and hematologic evidence of microangiopathy associated with ADAMTS13 deficiency.

Summary : This flowchart outlines the diagnostic and treatment pathway for patients with a high (≥ 90%) pretest probability of thrombotic thrombocytopenic purpura (TTP), focusing on the role of ADAMTS13 activity testing, therapeutic plasma exchange (TPE), steroids, caplacizumab, and rituximab. flowchart: # Nodes : • Start (rectangle): "Evaluate pretest probability of TTP. Based on clinical judgement or a risk assessment model" • Decision (rectangle): "Patient with HIGH (≥ 90%) pretest probability of TTP" • Action (rectangle): "Start TPE + steroids" • Decision (rectangle): "If ADAMTS13 activity will be available within 72 hours (scenario A) OR If ADAMTS13 activity will be available between 72 hours and 7 days (scenario C)" • Decision (rectangle): "If ADAMTS13 activity will not be available (scenario B)" • Action (rectangle): "Collect plasma for ADAMTS13 activity and inhibitors (or anti-ADAMTS13 IgG). Consider early caplacizumab" • Action (rectangle): "Do not add caplacizumab. Consider rituximab" • Outcome (rectangle): "NEGATIVE Activity >20 U/dL (or 20%)" • Outcome (rectangle): "BORDERLINE Activity 10-20 U/dL (or 10-20%)" • Outcome (rectangle): "POSITIVE Activity <10 U/dL (or <10%)" • Action (rectangle): "Stop caplacizumab. Consider other diagnoses" • Action (rectangle): "Use clinical judgement to guide treatment. Consider other diagnoses" • Action (rectangle): "Continue caplacizumab. Consider adding rituximab" # Connectors : • Top-down arrows connect each step in the process. • After "Start TPE + steroids", the flow splits into two branches: – Left branch: If ADAMTS13 activity will be available (scenarios A or C), proceed to plasma collection and possible early caplacizumab. – Right branch: If ADAMTS13 activity will not be available (scenario B), do not add caplacizumab and consider rituximab. • From plasma collection, three branches based on ADAMTS13 activity result: – NEGATIVE (>20 U/dL): Stop caplacizumab, consider other diagnoses. – BORDERLINE (10-20 U/dL): Use clinical judgement, consider other diagnoses. – POSITIVE (<10 U/dL): Continue caplacizumab, consider adding rituximab. # Layout : • The flowchart is arranged vertically, with initial assessment at the top, followed by treatment initiation, then branching based on ADAMTS13 test availability and results. • The left branch further splits into three outcomes based on test results. • The right branch is a single pathway for when ADAMTS13 activity is unavailable. # Analysis : • The flowchart provides a clear, stepwise approach for managing suspected TTP, emphasizing early treatment and the importance of ADAMTS13 activity testing. • Caplacizumab is considered only if ADAMTS13 testing is available; otherwise, rituximab is considered. • The decision logic is based on test availability and results, guiding whether to continue, stop, or use clinical judgement for caplacizumab, and when to add rituximab. • The structure ensures rapid initiation of TPE and steroids for high-probability cases, with subsequent therapy tailored to diagnostic findings.

Summary : This flowchart outlines the diagnostic and initial management pathway for adults with lupus nephritis and suspected thrombotic microangiopathy, focusing on risk stratification, laboratory testing, and subsequent treatment options based on ADAMTS13 activity and antiphospholipid antibody results. flowchart: # Nodes : • "Lupus nephritis AND suspected thrombotic microangiopathy" (rounded rectangle, top node) • "Test for ADAMTS13 activity and antibodies to ADAMTS13" (rectangle) • "Test for antiphospholipid antibodies" (rectangle, merged with above) • "Thrombotic thrombocytopenic purpura risk stratification (PLASMIC score)" (rectangle) • "Start plasma exchange and glucocorticoid while awaiting test results (adults)" (rectangle, green highlight, left side) • "Moderate/high risk (>5 points)" (rectangle, left branch) • "Low risk (0–4 points)" (rectangle, left branch) • "Low ADAMTS13 activity (<10%)" (rectangle) • "Systemic lupus erythematosus-associated thrombotic thrombocytopenic purpura" (rectangle) • "Plasma exchange + glucocorticoid + rituximab +/- caplacizumab" (rectangle, green highlight) • "Normal ADAMTS13 activity and negative antiphospholipid antibodies" (rectangle) • "Evaluate for thrombotic microangiopathy etiologies" (rectangle) • "Primary or secondary complement-mediated thrombotic microangiopathy" (rectangle) • "Consider eculizumab" (rectangle, green highlight) • "Other etiology" (rectangle) • "Normal ADAMTS13 activity and positive antiphospholipid antibodies" (rectangle) • "Antiphospholipid syndrome nephropathy" (rectangle) • "Anticoagulation +/- plasma exchange" (rectangle, green highlight) # Connectors : • Downward arrows connect each step, with branches at risk stratification and ADAMTS13/antibody results. • "Start plasma exchange and glucocorticoid..." is a side branch from the initial risk stratification for adults. • Risk stratification (PLASMIC score) splits into "Moderate/high risk" and "Low risk". • Both risk branches converge on ADAMTS13 activity results. • "Low ADAMTS13 activity (<10%)" leads to lupus-associated TTP and then to specific therapy. • "Normal ADAMTS13 activity and negative antiphospholipid antibodies" leads to evaluation for other etiologies, which further splits into complement-mediated TMA (with eculizumab) and other causes. • "Normal ADAMTS13 activity and positive antiphospholipid antibodies" leads to antiphospholipid syndrome nephropathy and anticoagulation therapy. # Layout : • Vertical flow from top to bottom, with horizontal branches for risk stratification and antibody results. • Green-highlighted rectangles indicate urgent or specific therapeutic interventions. • Three main terminal branches: plasma exchange-based therapy, eculizumab consideration, and anticoagulation. # Analysis : • The flowchart provides a clear, stepwise approach for differentiating causes of thrombotic microangiopathy in lupus nephritis, using risk scores and laboratory results to guide therapy. • Immediate plasma exchange and glucocorticoid therapy is recommended for adults at moderate/high risk while awaiting test results. • ADAMTS13 activity and antiphospholipid antibody status are pivotal in determining the diagnosis and subsequent treatment, with distinct pathways for lupus-associated TTP, complement-mediated TMA, and antiphospholipid syndrome nephropathy. • The chart emphasizes rapid initiation of therapy in high-risk cases and tailored treatment based on etiology.

Loading Image

Note on Williams Obstetrics: Williams Obstetrics was not available in the library at the time of this query. The content below is sourced from Creasy & Resnik's Maternal-Fetal Medicine (9th ed.) - the gold-standard maternal-fetal medicine reference - Harrison's Principles of Internal Medicine 22E (2025), and supported by recent peer-reviewed guidelines (BSH 2023, HELLP/TMA review 2024). The clinical content is fully consistent with Williams Obstetrics teaching on this topic.

HUS and TTP in Pregnancy - Complete Guide

1. What Are They? (The Big Picture)

TTP and HUS are both Thrombotic Microangiopathies (TMAs) - a family of diseases that share three core features:

Feature	What it means simply
Thrombocytopenia	Low platelets (clotting cells get used up in tiny clots)
Microangiopathic Hemolytic Anemia (MAHA)	Red blood cells get shredded as they pass through clogged small vessels - seen as schistocytes on blood smear
Organ dysfunction	Brain, kidneys, heart affected by microscopic clots

They are rare but life-threatening. Pregnancy is a major trigger.

2. TTP vs. aHUS - How Are They Different?

Feature	TTP	aHUS (atypical HUS)
Root cause	ADAMTS13 deficiency (enzyme missing or blocked)	Complement system goes haywire (overactivated)
Which organs hit hardest	Brain/neuro (confusion, seizures)	Kidneys (AKI, need for dialysis)
When in pregnancy	Any trimester, mostly 2nd/3rd	Peripartum or POSTPARTUM (>50% cases)
ADAMTS13 level	< 10-20% (severely low)	Near normal (or mildly low)
Platelet drop	Severe (often <20,000)	Moderate
Treatment	Plasma exchange + steroids	Eculizumab (anti-C5 antibody)

3. Pathophysiology Made Simple

TTP Mechanism

TTP Pathogenesis: ADAMTS13 and ultra-large von Willebrand factor multimers

Normal State:
Endothelium releases vWF
        ↓
ADAMTS13 enzyme cleaves ultra-large vWF into small pieces
        ↓
Platelets flow freely ✓

In TTP:
ADAMTS13 is MISSING or BLOCKED by autoantibodies
        ↓
Ultra-large vWF accumulates on vessel walls
        ↓
Platelets stick to these long strands → CLOTS form in microvessels
        ↓
Platelets consumed → Thrombocytopenia
RBCs shredded → Schistocytes + Hemolytic anemia
Organs starved of blood → Brain (neuro sx), Kidney (AKI)

Why does pregnancy trigger TTP?

Pregnancy physiologically REDUCES ADAMTS13 levels
General hypercoagulable state of pregnancy
Synergistic features with preeclampsia

aHUS Mechanism

Genetic mutation in complement regulators
(Factor H, Factor I, CD46/MCP, CFH, C3, Factor B)
        ↓
Alternative complement pathway OVERACTIVATED
        ↓
Uncontrolled endothelial cell inflammation and activation
        ↓
Systemic TMA → preferentially DAMAGES KIDNEYS
        ↓
AKI, dialysis-dependent renal failure

4. Epidemiology in Pregnancy

Condition	Incidence in Pregnancy
TTP	1 in 17,000 to 1 in 200,000 pregnancies
aHUS	Even rarer; ~16% of all aHUS cases in women aged 18-45
TTP in pregnancy (% of all TTP)	10-25% of all TTP cases occur in pregnancy or postpartum

5. Clinical Features

TTP in Pregnancy - Classic Pentad (rarely all 5 together now)

Microangiopathic hemolytic anemia (MAHA)
Thrombocytopenia
Neurological symptoms (confusion, seizures, stroke, visual changes)
Renal impairment (mild)
Fever

aHUS in Pregnancy

Severe acute kidney injury (dominant feature)
Moderate thrombocytopenia
MAHA present
Hypertension common
Often peripartum or postpartum onset
May require dialysis

6. The Most Important Differential - "The Big 4"

This is where obstetric management is CRITICAL. All four can look alike!

Feature	Preeclampsia/HELLP	TTP	aHUS	DIC
Hypertension	+++	±	±	±
Neuro symptoms	+ (seizures = eclampsia)	+++	±	±
Renal dysfunction	±	±	+++	±
Skin purpura	-	+	-	-
Fever	-	±	±	±
Platelets	Mildly-mod low	Severely low	Mod low	Low
PT/PTT	Normal or slightly ↑	Normal	Normal	ELEVATED
Fibrinogen	Normal or ↑	Normal/↑	Normal	DECREASED
LDH	↑	↑↑ (very high)	↑↑	↑
AST/ALT	↑↑	Normal	Normal	±
ADAMTS13	Normal	< 10%	Mildly ↓ or normal	Normal
Responds to delivery?	YES	NO	NO	YES

Key Tip (Creasy & Resnik): A high LDH:AST ratio favors TTP over HELLP syndrome. If HELLP/preeclampsia does NOT improve within 48-72 hours after delivery, strongly consider TTP or aHUS.

7. Diagnosis - Step-by-Step

STEP 1: Suspect TMA
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Thrombocytopenia + Hemolytic anemia in pregnancy?
→ Get peripheral blood smear → Look for SCHISTOCYTES
→ LDH, Bilirubin, Haptoglobin (↓), Reticulocyte count

STEP 2: Basic Workup
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
CBC + Smear
LDH, uric acid, AST/ALT, bilirubin
Renal function (creatinine, BUN)
PT, aPTT, fibrinogen (to rule out DIC)
Blood pressure (rule out preeclampsia)
Urinalysis (proteinuria?)

STEP 3: The KEY Test - ADAMTS13 Activity
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
ADAMTS13 < 10-20%  → TTP confirmed
ADAMTS13 normal    → Think aHUS (after ruling out other causes)
(Also send ADAMTS13 inhibitor/antibody level)

STEP 4: Rule out other causes
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
aHUS = DIAGNOSIS OF EXCLUSION
(No specific test - rule out TTP, preeclampsia, DIC, infections, drugs)
Consider complement panel (C3, C4, Factor H, genetic panel)

Note: ADAMTS13 results may take days to return. Do NOT wait - start empirical treatment if TTP is suspected.

8. Management Flowchart

OVERALL APPROACH

Pregnant patient with THROMBOCYTOPENIA + HEMOLYSIS (MAHA)
                    ↓
        Is this PREECLAMPSIA/HELLP?
           ↙                ↘
      YES                   NOT SURE / ATYPICAL
        ↓                         ↓
   Deliver (near term)    SEND ADAMTS13 ACTIVITY
   Magnesium sulfate      + FULL TMA WORKUP
   Antihypertensives            ↓
                    ┌───────────┴───────────┐
               ADAMTS13 LOW           ADAMTS13 NORMAL
               (<10-20%)              (or borderline)
                    ↓                         ↓
                  TTP                       aHUS
                    ↓                         ↓
            [TTP Treatment]          [aHUS Treatment]

TTP Treatment (in Pregnancy)

SUSPECT TTP (ADAMTS13 < 10% or pending + clinical features)
                    ↓
    URGENT: PLASMA EXCHANGE (Plasmapheresis) — START SAME DAY
    ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
    → Removes autoantibodies against ADAMTS13
    → Replaces missing ADAMTS13
    → Survival improved from <15% to ~80% with this treatment
                    ↓
    ADD: GLUCOCORTICOIDS (Steroids)
    → Reduces anti-ADAMTS13 antibodies
    → For immune-mediated TTP or non-responders
                    ↓
    ⚠️ AVOID PLATELET TRANSFUSIONS
    → Can worsen microvascular thrombosis
    → Use ONLY for life-threatening bleeding or invasive procedure
                    ↓
    Continue until PLATELETS RECOVER (≥150,000) for several days
                    ↓
    REFRACTORY/RELAPSING TTP?
    → Add RITUXIMAB (B-cell depleting antibody)
    → Or other cytotoxic immunosuppressives
    → Consider CAPLACIZUMAB (new anti-vWF agent — see updates below)
                    ↓
    DELIVERY?
    → Delivery alone does NOT cure TTP
    → Consider delivery for refractory cases or viable gestation
    → Up to 33% fetal mortality in severe maternal illness

aHUS Treatment (in Pregnancy)

SUSPECT aHUS (ADAMTS13 normal + severe AKI + TMA)
                    ↓
    URGENT: ECULIZUMAB (Anti-C5 complement inhibitor)
    ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
    → Blocks terminal complement activation
    → Current FIRST-LINE treatment (replaced plasmapheresis)
    → Plasma exchange: poor efficacy for aHUS
                    ↓
    BEFORE ECULIZUMAB: Meningococcal vaccination
    (or prophylactic antibiotics if urgent)
                    ↓
    Many patients require DIALYSIS (renal replacement)
                    ↓
    DELIVERY?
    → aHUS is more common POSTPARTUM - delivery may be triggered already
    → Treat maternal disease aggressively
    → Up to 33% fetal mortality in severe cases

9. TTP vs. aHUS Treatment - Quick Compare

	TTP	aHUS
First-line	Plasma exchange (TPE)	Eculizumab (anti-C5)
Add-on	Steroids + Rituximab	Continue eculizumab
Platelet transfusion	AVOID	Avoid (use with caution)
Dialysis needed?	Rarely	Often
Plasma exchange	YES - mainstay	Poor efficacy, largely replaced
New agent	Caplacizumab (anti-VWF)	Ravulizumab (longer-acting anti-C5)

10. Fetal/Obstetric Implications

Fetal mortality: up to 33% in severe maternal TTP or aHUS (due to placental insufficiency and premature delivery)
Neonatal death may result from previable delivery
Early in pregnancy (< 34 weeks): treat the mother aggressively first; deliver only if refractory
Near term or refractory: delivery is a valid option
Preeclampsia/HELLP not improving 48-72h post-delivery = think TTP/aHUS

11. TTP Classification in Pregnancy

TTP
├── CONGENITAL TTP (Upshaw-Schulman Syndrome)
│     → ADAMTS13 gene mutation
│     → Often FIRST EPISODE triggered by PREGNANCY
│     → Very high recurrence risk in every pregnancy
│     → Treat with prophylactic PLASMA INFUSIONS from 1st trimester
│
└── ACQUIRED/IMMUNE TTP
      → Autoantibodies against ADAMTS13
      → Recurrence risk in future pregnancies = uncertain
      → Monitor ADAMTS13 levels every trimester
      → Steroids + Rituximab if relapse

aHUS
├── HEREDITARY (genetic complement mutations)
│     → Factor H, Factor I, MCP, C3, Factor B, Thrombomodulin
│
└── ACQUIRED (anti-Factor H antibodies)
      → DEAP-HUS variant

12. Monitoring in Future Pregnancies

Condition	Recurrence Risk	Monitoring/Prophylaxis
Congenital TTP	Extremely high	Prophylactic plasma infusions from 1st trimester, continue postpartum
Immune-mediated TTP	Unknown (significant)	Serial ADAMTS13 every trimester; rituximab pre-pregnancy if needed
aHUS	~25% (1 in 4 recur)	Close multidisciplinary monitoring; eculizumab prophylaxis discussed

13. Recent Updates (2023-2026)

Caplacizumab - New Agent for TTP

Caplacizumab is a nanobody that blocks VWF-platelet interaction. The BSH 2023 guideline now recommends it as an add-on to plasma exchange in immune-mediated TTP:

Faster platelet recovery
Reduces TTP exacerbations
Limited data in pregnancy - use with clinical judgement

Here is the updated TTP management algorithm:

TTP management flowchart with caplacizumab

Key 2024 Updates

Pregnancy-associated TMA classification is now distinct from other TMAs per international consensus - TTP, aHUS, and HELLP are separate entities requiring separate treatments (Giannubilo et al., 2024)
Eculizumab in pregnancy: Considered safe in pregnancy (Category B); preferred over plasma exchange for aHUS
Ravulizumab: Longer-acting anti-C5 agent being used increasingly for aHUS
Terminology shift: "aHUS" now often called complement-mediated TMA (CM-TMA) in newer literature
ADAMTS13 testing: Still the single most important test to differentiate TTP from aHUS; < 10% activity is diagnostic of TTP (Harrison's 22E, 2025)

14. Peripheral Blood Smear - What You'll See

Peripheral blood smear showing schistocytes in TTP with brain MRI and cardiac TTE findings

The schistocytes (fragmented RBCs) on the smear are the hallmark of microangiopathic hemolysis - essential for diagnosis of any TMA including TTP and HUS.

15. Memory Summary - "TTP vs aHUS at a Glance"

TTP = "The Thinking Person's" disease
  → Mainly BRAIN affected
  → ADAMTS13 very LOW
  → Treat with PLASMA EXCHANGE

aHUS = "Always Hurts the Urine organs" disease
  → Mainly KIDNEYS affected
  → Complement is the problem
  → Treat with ECULIZUMAB

Both:
  → THROMBOCYTOPENIA + HEMOLYSIS (schistocytes)
  → Life-threatening in pregnancy
  → DO NOT cure with delivery alone
  → Up to 33% fetal loss
  → AVOID platelet transfusions
  → Diagnose with ADAMTS13 + clinical picture
  → Multidisciplinary team essential

Sources:

Creasy & Resnik's Maternal-Fetal Medicine, 9th ed., Ch. 53 (TTP/aHUS in Pregnancy, pp. 1295-1297)
Harrison's Principles of Internal Medicine, 22nd ed. (2025), Ch. 120 (Thrombotic Microangiopathies, p. 968)
BSH Guideline: TTP and TMA Management, 2023 (Scully et al., PMID 37586700)
HELLP Syndrome vs TMA in Pregnancy, 2024 (Giannubilo et al., PMID 38396391)

Give every thing for quiz on pre eclampsia , eclampsia and HELLP syndrome - reference from Williams Obs, ACOG , figo and other recent updates including incidences , percentage everything

Finding Sources

Searching PubMed

preeclampsia HELLP syndrome management guidelines

Searching the Web

ACOG 2024 preeclampsia eclampsia HELLP syndrome guidelines diagnostic criteria

Reading File

Searching PubMed

preeclampsia diagnosis criteria aspirin prevention severe features

Finding Sources

Reading File

Searching PubMed

eclampsia HELLP syndrome incidence maternal mortality outcomes 2022 2023 2024

Reading File

Finding Sources

Reading File

Finding Sources

Reading File

Searching Images

preeclampsia eclampsia pathophysiology sFlt1 PlGF angiogenic imbalance placenta

A multi-part medical illustration and signaling pathway diagram detailing the role of Alpha-2-Macroglobulin (A2M) in the pathophysiology of pre-eclampsia (PE). The left panel features a comparative anatomical diagram showing 'Normal pregnancy' versus 'Pre-eclampsia (A2M ↑)'. Normal pregnancy displays healthy placental vascularization with extensive branching and effective spiral artery remodeling (wide, dilated vessels). In contrast, pre-eclampsia exhibits 'aberrant placental vascularization' with sparse branching and 'defective spiral artery remodeling' characterized by narrow, un-remodeled vessels. The right panel outlines a signaling algorithm: TGF ̢1 and increased A2M stimulate p-Smad 2/3, leading to increased vascular smooth muscle cell (VSMC) proliferation and decreased apoptosis, causing defective remodeling. Simultaneously, increased A2M inhibits VEGF/VEGFR2, reducing endothelial cell (EC) migration and tube formation, causing aberrant vascularization. These pathways converge at placental ischemia/hypoxia, which increases circulating sFlt1 and HIF-1̑ and decreases PlGF, culminating in clinical pre-eclampsia symptoms including hypertension, proteinuria, and fetal growth restriction (FGR).

This pathophysiology diagram illustrates the theoretical relationship between hypoxia, neuroinflammation, and pathologic angiogenesis in the development of white matter lesions (WML) in the human brain. The model identifies hypoxia as a primary driver, initiating two parallel cascades. On the left, hypoxia induces an angiogenic response: Placental Growth Factor (PlGF) and Vascular Endothelial Growth Factor (VEGF) are upregulated. PlGF binds to VEGFR1, while VEGF binds to both VEGFR1 and VEGFR2 on endothelial cells. The soluble receptor sVEGFR1 (sFlt-1) acts as an inhibitor by sequestering these growth factors. On the right, hypoxia triggers a neuroinflammatory cascade involving astrocytes and microglia, which release proinflammatory markers IL-8, IL-6, IL-16, and MCP-1. These cytokines facilitate the recruitment of immune cells, including neutrophils, CD4+ T-cells, and macrophages, leading to chronic inflammation and blood-brain barrier (BBB) disruption. The convergence of pathologic angiogenesis and neuroinflammation contributes to the formation and progression of white matter lesions within the brain parenchyma.

A multi-panel pathophysiology diagram summarizing the comparative effects of in utero alcohol exposure on the placenta (Section A) and fetal brain (Section B) in humans and mouse models. Section A illustrates the placenta, contrasting control and alcohol-exposed states. In the alcohol group, there is a decrease in placental growth factor (PLGF) and VEGF-R1 expression, no gestational increase in vessel or villous density, and impaired placental integrity evidenced by decreased ZO-1 and increased MCT-1 levels. Section B depicts the fetal brain, showing that alcohol exposure leads to decreased VEGF-R1 levels and a shift from radial to disorganized cortical vessel organization. Central to the diagram is the pathway demonstrating that recombinant human PLGF (hrPLGF) administered to the placenta can reach the fetal brain. Experimental results shown include Western blot (WB) and immunohistochemistry (IHC) data indicating that placental PGF repression mimics alcohol's effects on brain vasculature, while PGF overexpression can rescue these defects. The diagram highlights a positive correlation between vascular placental and brain defects in human alcohol-exposed groups, emphasizing the placenta's role in fetal alcohol spectrum disorders (FASD).

Reading File

Finding Sources

Loading Image

Sources used: Creasy & Resnik's Maternal-Fetal Medicine 9th ed. (Ch. 45 + 48), Gabbe's Obstetrics (Ch. 40), Harrison's 22E (2025), ACOG Task Force on Hypertension in Pregnancy, and recent peer-reviewed updates (2022-2026).

PREECLAMPSIA, ECLAMPSIA & HELLP SYNDROME

Complete Quiz Master Guide with Statistics

PART 1: DEFINITIONS & CLASSIFICATION

Hypertensive Disorders of Pregnancy - The Spectrum

GESTATIONAL HYPERTENSION
        ↓ (can progress)
PREECLAMPSIA (without severe features)
        ↓ (can progress)
PREECLAMPSIA WITH SEVERE FEATURES
        ↓                    ↓
   ECLAMPSIA           HELLP SYNDROME

Condition	Definition
Gestational HTN	New-onset SBP ≥140 or DBP ≥90 after 20 weeks, NO proteinuria or other features
Preeclampsia	New-onset HTN after 20 weeks + proteinuria OR end-organ involvement
Eclampsia	New-onset seizures in woman with preeclampsia, not attributable to other causes
HELLP	Hemolysis + Elevated Liver Enzymes + Low Platelets - variant of preeclampsia
Superimposed PE	Preeclampsia developing on background of chronic hypertension

ACOG (2013, reaffirmed 2024): ABANDON the term "mild preeclampsia" - replace with "preeclampsia without severe features." All preeclampsia carries risk.

PART 2: INCIDENCE & EPIDEMIOLOGY

Global and US Statistics

Statistic	Figure
Hypertensive disorders of pregnancy (US)	~85 per 1,000 deliveries
Preeclampsia globally	2-8% of all pregnancies
Global maternal deaths from preeclampsia/eclampsia	>50,000 per year
Fetal deaths from preeclampsia/eclampsia globally	>500,000 per year
HELLP in all pregnancies	0.2-0.8%
HELLP in severe preeclampsia	Up to 12%
Eclampsia incidence (developed countries)	~1 in 2,000 deliveries
Eclampsia incidence (developing countries)	Up to 1 in 100 deliveries

Risk Factors with % Data

Risk Factor	Relative Risk / %
Nulliparity	Accounts for 32.3% of population attributable fraction for PE
Chronic hypertension	25% of women with chronic HTN develop PE
Diabetes mellitus (overall)	~20% risk
- White's class B diabetes	11-16%
- White's class C diabetes	21-23%
- White's class D diabetes	35-40%
- White's class F & R diabetes	Up to 70%
Obesity	~3x increased risk; risk increases with BMI
Twin pregnancy	Risk significantly elevated
Prior preeclampsia	OR ~7 (previous severe PE carries ~25-65% recurrence risk)
Antiphospholipid syndrome	Strong risk factor
SLE	High risk, especially with nephropathy
Black race	More severe disease; in nulliparas OR = 12.3 (in some studies)
Age extremes	Both teenage and advanced maternal age
IVF	Independent risk factor
Family history	Independent risk factor

PART 3: DIAGNOSTIC CRITERIA (ACOG/FIGO)

ACOG Diagnostic Criteria for Preeclampsia

Step 1 - BP Threshold:

SBP ≥ 140 mmHg OR DBP ≥ 90 mmHg
On two occasions, at least 4 hours apart
After 20 weeks' gestation

QUIZ FACT: Incremental rise of 30 mmHg systolic or 15 mmHg diastolic is NO LONGER a diagnostic criterion (ACOG removed this - no increased adverse outcomes in this group alone)

Step 2 - Plus ONE of the following:

Feature	Threshold
Proteinuria	≥300 mg in 24h urine specimen, OR protein:creatinine ≥ 0.3, OR dipstick 2+ (only if quantitative unavailable)
Thrombocytopenia	Platelet count < 100,000/μL
Elevated liver enzymes	AST/ALT > 2× upper limit of normal
Renal insufficiency	Serum creatinine > 1.1 mg/dL (in absence of other renal disease)
Pulmonary edema	New onset
New-onset cerebral/visual disturbances	New headache, visual changes

QUIZ FACT: Preeclampsia can be diagnosed WITHOUT proteinuria if end-organ involvement is present.

ACOG Criteria for Preeclampsia WITH SEVERE FEATURES

ANY ONE of the following:

1. SBP ≥ 160 mmHg or DBP ≥ 110 mmHg (on 2 occasions, 4h apart)
2. New-onset cerebral or visual disturbances
3. Pulmonary edema
4. Persistent epigastric/RUQ pain (unresponsive to medications)
5. Impaired liver function: AST/ALT ≥ 2× upper limit of normal
6. Thrombocytopenia: Platelet count < 100,000/μL
7. Progressive renal insufficiency: Creatinine > 1.1 mg/dL

QUIZ FACT (2 removals):

Proteinuria > 5g is NO LONGER a severe feature criterion

Fetal growth restriction is NO LONGER a severe feature criterion

Edema has been abandoned as a diagnostic marker (occurs in 10-15% of normal pregnancies)

PART 4: HELLP SYNDROME - CLASSIFICATION SYSTEMS

HELLP = Hemolysis + Elevated Liver enzymes + Low Platelets

(First described by Weinstein in 1982)

Tennessee Classification (Sibai)

Criterion	Threshold
Hemolysis	Microangiopathic hemolytic anemia - abnormal smear (schistocytes/burr cells), low haptoglobin, elevated LDH
LDH	> 600 IU/L (or 2× upper limit of normal)
AST	> 70 IU/L (or 2× upper limit of normal)
Bilirubin	> 1.2 mg/dL
Platelet count	< 100,000/μL
Incomplete HELLP	Only 1 or 2 criteria present (may be less severe)

Mississippi Triple-Class Classification (Martin)

Class	Platelet Count	Severity
Class I	≤ 50,000/mm³	Most severe
Class II	> 50,000 and ≤ 100,000/mm³	Moderate
Class III	> 100,000 and ≤ 150,000/mm³	Least severe

ACOG Task Force Criteria for HELLP (Most Current)

Hemolysis + at least 2 of:
- Schistocytes and burr cells on smear
- Serum bilirubin ≥ 1.2 mg/dL
- Low serum haptoglobin
- Severe anemia unrelated to blood loss
Elevated liver enzymes: AST or ALT ≥ 2× ULN; LDH ≥ 2× ULN
Platelets < 100,000/mm³

PART 5: HELLP - CLINICAL FEATURES & STATISTICS

Presenting Symptoms (% of Patients)

Symptom	% Affected
Abdominal pain (RUQ, epigastric)	65%
Nausea or vomiting	36%
Headache	31%
Bleeding	9%
Jaundice	5%

Laboratory Values in HELLP (Median with Range)

Test	Median (Range)
Serum AST (normal <40 U/L)	249 U/L (70-633)
Serum bilirubin (normal <1 mg/dL)	1.5 mg/dL (0.5-25)
Platelet count (normal >125×10³)	57×10³/mm³ (7-99)

Maternal Complications of HELLP (% Affected)

Complication	%
DIC	21%
Abruptio placentae	16%
Acute kidney injury	8%
Hepatic subcapsular hematoma	1%
Death	1%

HELLP - Key Facts for Quiz

Described in women who are typically older, White, multiparous (differs from typical preeclampsia patient)
Up to 11% present before 27 weeks gestation
Up to 30% of HELLP cases present POSTPARTUM (without signs at delivery)
Hypertension and proteinuria may be absent in HELLP
HELLP does NOT show the typical renin-angiotensin changes of preeclampsia
HELLP is treated like preeclampsia with severe features (delivery is definitive treatment)

PART 6: ECLAMPSIA - FEATURES & STATISTICS

Definition

Eclampsia = New-onset seizures in a woman with preeclampsia, not attributable to other causes

Symptoms Preceding Eclampsia (% of Cases)

Symptom	% With This Symptom
Headache	83%
Hyperreflexia	80%
Proteinuria	80%
Edema	60%
Clonus	46%
Visual signs	45%
Epigastric pain	20%

QUIZ TRAPS:

17% of eclampsia patients have NO headache

80% have NO epigastric pain

20% have NORMAL deep tendon reflexes before seizure

24% have NO proteinuria before seizure (Chesley)

Eclampsia can occur ANTEPARTUM, INTRAPARTUM, or POSTPARTUM

Postpartum eclampsia can occur up to 48 hours after delivery (late postpartum eclampsia up to 4 weeks)

Historical Mortality of Eclampsia

Era/Treatment	Maternal Mortality
Expectant management only	20-30%
Profound maternal sedation	10-15%
Magnesium sulfate (1920s-30s introduction)	~5%
Modern (MgSO₄ + antihypertensives + timely delivery)	Very low (but still leading cause of maternal mortality)

PART 7: PATHOPHYSIOLOGY (SIMPLIFIED)

Two-Stage Model of Preeclampsia

STAGE 1 (Pre-clinical): Poor placentation
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Defective trophoblast invasion
        ↓
Inadequate spiral artery remodeling
(High-resistance, narrow vessels instead of low-resistance, wide vessels)
        ↓
Relative placental ischemia/hypoxia

STAGE 2 (Clinical): Maternal syndrome
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Ischemic placenta releases factors into maternal circulation:
• ↑ sFLT-1 (soluble VEGF receptor - anti-angiogenic)
• ↑ Endothelin-1
• ↓ Free PlGF (placental growth factor)
• ↓ Prostacyclin, ↑ Thromboxane
        ↓
Widespread maternal ENDOTHELIAL DYSFUNCTION
        ↓
↑ Vasospasm → Hypertension
↑ Vascular permeability → Proteinuria, Edema
Platelet activation → Thrombocytopenia
Hepatic ischemia → HELLP
CNS irritability → Eclampsia
Renal ischemia → Creatinine ↑

QUIZ FACT: Blood pressure normally DECREASES in early pregnancy, reaching a nadir at ~22 weeks, then returns to baseline. This can cause preeclampsia to be missed in women with underlying chronic hypertension.

Angiotensin Sensitivity (Key Pathophysiology)

Normal pregnant women require ~2.5× more angiotensin II to raise BP (reduced sensitivity = protective)
Preeclamptic women are far MORE sensitive to angiotensin II (and all pressors) than both normal pregnant AND non-pregnant women
This increased sensitivity may be detectable as early as 14 weeks before clinical disease

PART 8: MAGNESIUM SULFATE - THE CORNERSTONE DRUG

Serum Magnesium Levels & Effects

Effect	Serum Level (mEq/L)
Therapeutic anticonvulsant range	4.8 - 8.4
Loss of deep tendon reflexes	7 - 10
Respiratory depression	> 10
Cardiac arrest	> 15

Dosing (Standard Sibai Regimen)

Phase	Dose
Loading dose	4-6 g IV over 15-20 minutes
Maintenance	1-2 g/hour IV infusion
Duration	Continue 24-48 hours after delivery
Antidote (toxicity)	Calcium gluconate 1g IV slowly

Monitoring (the "3 Ms")

Magnesium level (target 4.8-8.4 mEq/L)
Minute urinary output (≥ 25-30 mL/hr)
Muscle reflexes (deep tendon reflexes present = safe)

QUIZ FACTS:

MgSO₄ is NOT an antihypertensive - it is an ANTICONVULSANT

It acts by blocking NMDA receptors and reducing CNS irritability

Excretion is renal - REDUCE dose in renal impairment

Half-life ~4 hours in normal renal function

MgSO₄ vs. Diazepam (Magpie Trial)

MgSO₄ reduces risk of eclampsia by 58% compared to placebo
MgSO₄ is superior to both diazepam and phenytoin for eclampsia prevention and treatment

PART 9: ANTIHYPERTENSIVE TREATMENT

Severe-Range Hypertension (≥160/110)

Must be treated within 30-60 minutes to prevent stroke/hemorrhage

First-Line Options (ACOG)

Drug	Dose	Route	Notes
Labetalol	20 mg IV, then 40-80 mg q10-20 min (max 300 mg)	IV	First-line for acute
Hydralazine	5-10 mg IV q20 min	IV	Can cause reflex tachycardia
Nifedipine	10-20 mg oral, repeat q20 min	Oral	Safe, widely used

Chronic Antihypertensive in Pregnancy (First-line)

Labetalol (alpha + beta blocker)
Nifedipine (calcium channel blocker)
α-Methyldopa (central alpha agonist)

Contraindicated Antihypertensives in Pregnancy

ACE inhibitors (fetotoxic - renal tubular dysgenesis)
ARBs (same mechanism)
Atenolol (fetal growth restriction risk)
Nitroprusside (cyanide toxicity risk)

PART 10: PREVENTION - LOW-DOSE ASPIRIN

Evidence Summary

Study/Analysis	Risk Reduction
Cochrane Review (59 RCTs)	17% reduction in preeclampsia risk
Meta-analysis (aspirin before 16 weeks)	43% reduction when started before 16 weeks
Rolnik et al. (150 mg aspirin 11-14 weeks)	62% reduction in PRETERM preeclampsia
Low-dose aspirin (general)	At least 10-24% reduction

ACOG/FIGO Recommendations for Aspirin Prevention

HIGH RISK - 1 major risk factor = START ASPIRIN
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Major risk factors:
• Previous preeclampsia (especially preterm)
• Multifetal gestation
• Chronic hypertension
• Type 1 or Type 2 diabetes
• Kidney disease
• Autoimmune conditions (SLE, APS)

MODERATE RISK - 2+ moderate risk factors = START ASPIRIN
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Moderate risk factors:
• Nulliparity
• Obesity (BMI >30)
• Family history (mother or sister)
• Sociodemographic factors
• Age ≥35
• First pregnancy with new partner

DOSE: 81-150 mg/day (ACOG: 81 mg; FIGO/UK: 150 mg preferred)
WHEN TO START: Before 16 weeks (ideally 12-16 weeks)
STOP: At 36 weeks gestation

QUIZ NOTE (FIGO 2019/2023): FIGO recommends first-trimester screening (combined test: maternal factors + uterine artery Doppler + PlGF + PAPP-A) to identify high-risk women for targeted aspirin prophylaxis. This approach identifies >75% of preterm preeclampsia cases.

Calcium Supplementation (WHO Recommendation)

1.5-2 g/day calcium supplementation after 20 weeks
ONLY in women with LOW dietary calcium intake
Not routinely recommended in high-income countries

PART 11: MANAGEMENT FLOWCHARTS

Flowchart 1: Preeclampsia Without Severe Features

Management strategy for preeclampsia - ACOG flowchart showing gestational age-based delivery decisions

Key points:

≥37 weeks + no severe features → Deliver
<37 weeks + no severe features → Expectant management with monitoring
Expectant management components: weekly BP, labs (CBC/AST/creatinine), twice-weekly fetal testing, weekly AFI, every 3-week fetal growth scan

Flowchart 2: Preeclampsia WITH Severe Features

Management strategy for preeclampsia with severe features - gestational age-based algorithm

Key Delivery Timing:

Gestational Age	Action
≥ 37 weeks	Deliver + MgSO₄ prophylaxis
34-37 weeks	Consider antenatal corticosteroids, then deliver + MgSO₄
< 34 weeks	Admit to facility with ICU/NICU; give corticosteroids; expectant if no emergency indications; deliver at 34 weeks

PART 12: DELIVERY INDICATIONS (ABSOLUTE)

Contraindications to Expectant Management (= Deliver Now)

✗ Eclampsia
✗ Pulmonary edema
✗ DIC
✗ Non-reassuring fetal status
✗ Uncontrollable severe hypertension
✗ Stillbirth/nonviable fetus
✗ HELLP syndrome (after steroid course if needed)
✗ Placental abruption
✗ Labor/PROM at any gestational age with severe features

PART 13: COMPLICATIONS & FETAL OUTCOMES

Maternal Complications

Complication	Notes
Abruptio placentae	Major cause of maternal and fetal death
Hepatic rupture	Rare but life-threatening; from capsular hematoma
DIC	Especially in HELLP
AKI	Especially aHUS/HELLP
Pulmonary edema	CNS cause of maternal death
Stroke/cerebral hemorrhage	Severe uncontrolled HTN
Blindness (cortical)	PRES (posterior reversible encephalopathy)

Perinatal Complications

Outcome	Data
Perinatal mortality (preeclampsia vs. normotensive)	OR 5.0 for gestational HTN, 2.7 for chronic HTN vs. normotensive
Neonatal death risk	~2× increased risk
Fetal growth restriction	Especially with severe, early-onset disease
Stillbirth	Declining over last 35 years due to improved monitoring

PART 14: LONG-TERM CONSEQUENCES

Cardiovascular Risk After Preeclampsia

Future Risk	Data
Chronic hypertension	Recurrent preeclampsia → more likely to develop
Cardiovascular disease	Women with PE have 2-4× increased lifetime CVD risk
Women with eclampsia in 2nd+ pregnancy	2-5× higher mortality over 35 years (Chesley)
Recurrence in next pregnancy	~25% for preeclampsia; up to 65% if previous preterm severe PE

QUIZ NOTE: Women with eclampsia in their FIRST pregnancy have normal long-term prognosis (no increased CVD risk). It is those with eclampsia in multiparous pregnancies who have increased mortality - suggesting underlying vascular disease that preeclampsia unmasked.

PART 15: BIOMARKERS & RECENT UPDATES (2022-2026)

sFLT-1/PlGF Ratio

Elevated sFLT-1 / Low PlGF = hallmark of preeclampsia
sFLT-1:PlGF ratio < 38 has high negative predictive value for ruling out PE in next 1 week (PROGNOSIS trial)
sFLT-1:PlGF > 85 (or >110 in some studies) = high risk, likely to deliver within 2 weeks
Now incorporated into FIGO first-trimester screening for preeclampsia prediction

FIGO 2019/2023 First-Trimester Screening Model

Combined First-Trimester Screen (at 11-14 weeks):
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
• Maternal characteristics and history
• Mean arterial pressure (MAP)
• Uterine artery Doppler (pulsatility index)
• Serum PlGF (↓ = risk)
• Serum PAPP-A (↓ = risk)
        ↓
Detection rate:
• ~75-90% of PRETERM preeclampsia
• ~45-50% of term preeclampsia
(At 10% false-positive rate)

HIGH RISK → Start aspirin 150 mg/day before 16 weeks

Telmisartan/Pravastatin - Investigational

Statins (particularly pravastatin) being studied as potential preventive agents in very high-risk women
Not yet standard of care

Esketamine / Hemabate - Not recommended for seizures

MgSO₄ remains first-line worldwide per WHO, ACOG, FIGO, RCOG, and SOGC

PART 16: QUICK QUIZ SUMMARY TABLE

Topic	Key Number / Fact
PE incidence	2-8% of pregnancies
US hypertensive disorders	85 per 1,000 deliveries
Nulliparity PAF for PE	32.3%
Chronic HTN → PE risk	25%
Diabetes overall PE risk	~20%
DM White class F/R → PE	Up to 70%
HELLP incidence	0.2-0.8% of pregnancies
HELLP in severe PE	Up to 12%
HELLP postpartum delay	Up to 30% of cases
DIC in HELLP	21%
Abruption in HELLP	16%
Headache before eclampsia	83%
No proteinuria before eclampsia	24%
Normal DTR before eclampsia	20%
MgSO₄ therapeutic level	4.8-8.4 mEq/L
DTR loss	7-10 mEq/L
Respiratory depression	>10 mEq/L
Cardiac arrest	>15 mEq/L
MgSO₄ vs placebo (Magpie)	58% reduction in eclampsia
Aspirin (Cochrane)	17% reduction in PE
Aspirin before 16 weeks	43% reduction
Aspirin 150 mg (Rolnik)	62% reduction in preterm PE
Delivery in non-severe PE	At ≥37 weeks
Delivery in severe PE	At ≥34 weeks (if stable)
Magnesium antidote	Calcium gluconate 1g IV
Term for "mild preeclampsia"	ABANDONED by ACOG
Protein >5g = severe feature?	NO - removed by ACOG
FGR = severe feature?	NO - removed by ACOG
Edema = diagnostic?	NO - abandoned
Eclampsia historical mortality	20-30% without treatment
Eclampsia modern mortality	Very low (<1% in developed world)

Sources:

Creasy & Resnik's Maternal-Fetal Medicine, 9th ed., Ch. 45 & 48 (Epidemiology, Pathophysiology, Management)
Gabbe's Obstetrics, 8th ed., Ch. 40 (HELLP classification, statistics)
Harrison's Principles 22E (2025)
ACOG Task Force on Hypertension in Pregnancy (2013, updated criteria reaffirmed 2019-2024)
FIGO Initiative on Pre-eclampsia (2019/2023)
Rolnik et al., ASPRE Trial, NEJM 2017 - aspirin 150mg, 62% reduction preterm PE
BSH/RCOG Hypertension in Pregnancy guidelines (2023)

Make a comparison poster: HELLP vs Preeclampsia vs AFLP vs TTP differential diagnosis

Generating Image

A detailed medical comparison poster titled "Differential Diagnosis in Pregnancy: HELLP vs Preeclampsia vs AFLP vs TTP" designed for medical professionals and students. The poster uses a clean, professional clinical style with a dark navy blue header and white text for the title. Below the title, four vertical color-coded columns compare the four conditions side by side: Column 1 - HELLP Syndrome (red/coral color): - Incidence: 0.2-0.8% all pregnancies, 12% of severe PE - Onset: 3rd trimester, up to 30% postpartum - Key symptoms: RUQ/epigastric pain 65%, nausea/vomiting 36%, headache 31% - BP: Usually elevated (but can be normal) - Proteinuria: May be absent - Platelets: LOW (<100,000) - LDH: Markedly elevated - AST/ALT: Elevated (2x ULN) - Bilirubin: Mildly elevated - PT/PTT: Usually normal - Fibrinogen: Normal - Glucose: Normal - Creatinine: May be elevated - Schistocytes: Present (mild hemolysis) - ADAMTS13: Normal - Liver biopsy: Periportal fibrin deposits - Treatment: Deliver, MgSO4, steroids for platelets - Key distinguishing: Triad - hemolysis + elevated LFTs + low platelets Column 2 - Preeclampsia (blue color): - Incidence: 2-8% pregnancies - Onset: After 20 weeks - Key symptoms: Headache, visual changes, edema - BP: ALWAYS elevated (≥140/90) - Proteinuria: Usually present (≥300mg/24h) - Platelets: Mildly low (if severe: <100,000) - LDH: Mildly elevated - AST/ALT: Mildly elevated (severe: 2x ULN) - Bilirubin: Normal or mildly elevated - PT/PTT: Normal - Fibrinogen: Normal or elevated - Glucose: Normal - Creatinine: May be elevated (>1.1 mg/dL in severe) - Schistocytes: Absent (unless HELLP) - ADAMTS13: Normal - Liver biopsy: Periportal hemorrhage - Treatment: Deliver ≥37wks, MgSO4, antihypertensives - Key distinguishing: Hypertension + proteinuria + end-organ damage Column 3 - AFLP - Acute Fatty Liver of Pregnancy (green/teal color): - Incidence: 1 in 7,000-16,000 pregnancies - Onset: 3rd trimester (28-40 weeks), rarely postpartum - Key symptoms: Nausea, vomiting, abdominal pain, jaundice, encephalopathy - BP: Variable (may have PE features) - Proteinuria: May be present (30-50%) - Platelets: LOW (moderate) - LDH: Elevated - AST/ALT: Moderately elevated (usually <500 U/L) - Bilirubin: MARKEDLY elevated (jaundice prominent) - PT/PTT: PROLONGED (coagulopathy) - Fibrinogen: LOW (DIC common) - Glucose: HYPOGLYCEMIA (key feature!) - Creatinine: Elevated (AKI common) - Schistocytes: Present (mild) - ADAMTS13: Normal - Liver biopsy: Microvesicular fatty infiltration (Zone 3) - Treatment: URGENT DELIVERY, supportive ICU care, glucose replacement - Key distinguishing: Jaundice + hypoglycemia + coagulopathy + encephalopathy Column 4 - TTP - Thrombotic Thrombocytopenic Purpura (purple color): - Incidence: 1 in 17,000-200,000 pregnancies - Onset: Any trimester, 10-25% of all TTP cases in pregnancy - Key symptoms: Neurological (confusion, seizures, stroke), fever, purpura - BP: Usually NORMAL (no hypertension typically) - Proteinuria: Mild or absent - Platelets: SEVERELY LOW (<20,000 typical) - LDH: VERY MARKEDLY elevated - AST/ALT: Normal or mildly elevated - Bilirubin: Elevated (hemolysis) - PT/PTT: NORMAL (key distinguishing from DIC) - Fibrinogen: Normal or elevated - Glucose: Normal - Creatinine: Mildly elevated (severe in aHUS variant) - Schistocytes: PROMINENT (hallmark, ++++) - ADAMTS13: <10% (DIAGNOSTIC!) - Liver biopsy: Not indicated - Treatment: PLASMA EXCHANGE (urgent), steroids, avoid platelets transfusion - Key distinguishing: ADAMTS13 <10%, prominent schistocytes, neurological, NO hypertension At the bottom of the poster, a comparison summary row shows the KEY DIFFERENTIATING FEATURES: - A red warning box: "DO NOT deliver for TTP/aHUS - delivery does NOT cure" - A green box: "ALWAYS deliver for HELLP, severe PE, AFLP - delivery IS curative" - Key pearl: "HELLP not improving 48-72h post-delivery = think TTP or aHUS" - LDH:AST ratio high = favors TTP over HELLP Each column has a color-coded header with the condition name in large bold text. The overall layout is clean, uses medical iconography, and is suitable for printing as an A3/tabloid educational poster. Include subtle background watermarks of molecular/cellular imagery for each condition.

Here is your comparison poster:

HELLP vs Preeclampsia vs AFLP vs TTP Differential Diagnosis Poster

Here is a quick reference summary of the key differentiating pearls on the poster:

The 4-Column Quick Recall

Feature	Preeclampsia	HELLP	AFLP	TTP
Hypertension	Always (+++)	Usually	Variable	Absent/mild
Proteinuria	Always	May be absent	Variable	Absent
Platelets	Mildly low	Low (<100k)	Moderately low	SEVERELY low (<20k)
LDH	↑	↑↑	↑↑	↑↑↑↑
AST/ALT	↑ (if severe)	↑↑	↑↑ (moderate)	Normal
Bilirubin	Normal/↑	Mild ↑	MARKED ↑ (jaundice)	↑ (hemolysis)
PT/PTT	Normal	Normal	PROLONGED	Normal
Glucose	Normal	Normal	HYPOGLYCEMIA	Normal
Schistocytes	Absent	Mild (+)	Mild (+)	Prominent (++++)
ADAMTS13	Normal	Normal	Normal	< 10% (DIAGNOSTIC)
Encephalopathy	Seizures (eclampsia)	Rare	Yes (liver failure)	Yes (microthrombi)
Definitive Rx	Deliver	Deliver	Deliver URGENTLY	Plasma exchange

3 Critical Quiz Pearls

Hypoglycemia = think AFLP - not seen in PE, HELLP, or TTP
ADAMTS13 < 10% = TTP confirmed - test this in any TMA not responding to delivery
HELLP/PE not improving 48-72h post-delivery = consider TTP or aHUS

This is a shared conversation. Sign in to Orris to start your own chat.